Masticable ingestible product and communication system therefor

ABSTRACT

An apparatus includes a food product, at least one ingestible device associated with the food product to communicate information and at least one coating material surrounding the at least one ingestible device is disclosed. The ingestible device is associated with an ingestible medication to be ingested in conjunction with the food product. The coating is configured to release the at least one ingestible device upon the occurrence of an event.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No.61/929,854, filed Jan. 21, 2014, entitled MASTICABLE INGESTIBLE PRODUCTAND COMMUNICATION SYSTEM THEREFOR, the disclosure of which isincorporated in its entirety by this reference.

This application is also related to the following U.S. applicationsfiled on Jul. 11, 2011, the disclosures of which are incorporate hereinby reference: U.S. application Ser. No. 13/180,516, filed Jul. 11, 2011and entitled COMMUNICATION SYSTEM WITH REMOTE ACTIVATION; U.S.application Ser. No. 13/180,525 filed on Jul. 11, 2011 and entitledCOMMUNICATION SYSTEM WITH ENHANCED PARTIAL POWER AND METHOD OFMANUFACTURING SAME; U.S. application Ser. No. 13/180,498, filed Jul. 11,2011 and entitled COMMUNICATION SYSTEM WITH MULTIPLE TYPES OF POWER;U.S. application Ser. No. 13/180,538, filed Jul. 11, 2011 and entitledCOMMUNICATION SYSTEM USING POLYPHARMACY CO-PACKAGED MEDICATION DOSINGUNIT; U.S. application Ser. No. 13/180,539, filed Jul. 11, 2011 andentitled COMMUNICATION SYSTEM USING AN IMPLANTABLE DEVICE; U.S.Application Publication No. 2012/0062379A1, filed Jul. 11, 2011,published Mar. 15, 2012, and entitled COMMUNICATION SYSTEM INCORPORATEDIN AN INGESTIBLE PRODUCT, the disclosures of which are hereinincorporated by reference.

FIELD

The present invention is related to masticable ingestible products andcommunication systems for detection of an event. More specifically, thepresent disclosure includes a system that includes a device forassociation with ingestible ingredients or products that can be combinedwith food products and pharmaceuticals agents and can survive themastication process.

INTRODUCTION

Ingestible devices that include electronic circuitry have been proposedfor use in a variety of different medical applications, including bothdiagnostic and therapeutic applications. These devices typically requirean internal power supply for operation. Examples of such ingestibledevices are ingestible electronic capsules which collect data as theypass through the body, and transmit the data to an external receiversystem. An example of this type of electronic capsule is an in-vivovideo camera. The swallowable capsule includes a camera system and anoptical system for imaging an area of interest onto the camera system.The transmitter transmits the video output of the camera system and thereception system receives the transmitted video output. Other examplesinclude an ingestible imaging device, which has an internal andself-contained power source, which obtains images from within bodylumens or cavities. The electronic circuit components of the device areenclosed by an inert indigestible housing (e.g. glass housing) thatpasses through the body internally. Other examples include an ingestibledata recorder capsule medical device. The electronic circuits of thedisclosed device (e.g. sensor, recorder, battery etc.) are housed in acapsule made of inert materials.

In other examples, fragile radio frequency identification (RFID) tagsare used in drug ingestion monitoring applications. In order for theRFID tags to be operational, each requires an internal power supply. TheRFID tags are antenna structures that are configured to transmit aradio-frequency signal through the body.

The problem these existing devices pose is that the power source isinternal to device and such power sources are costly to produce andpotentially harmful to the surrounding environment if the power sourceleaks or is damaged. Additionally, having antennas extending from thedevice is a concern as related to the antennas getting damaged orcausing a problem when the device is used in-vivo. Therefore, what isneeded is suitable system with circuitry that eliminates the need for aninternal power source and antennas.

SUMMARY

The present disclosure includes a system for producing a uniquesignature that indicates the occurrence of an event. The system includescircuitry and components that can be placed within certain environmentsthat include a conducting fluid. One example of such an environment isinside a container that houses the conducting fluid, such as a sealedbag with a solution, which includes an IV bag. Another example is withinthe body of a living organism, such as an animal or a human. The systemsare ingestible and/or digestible or partially digestible. The systemincludes dissimilar materials positioned on the framework such that whena conducting fluid comes into contact with the dissimilar materials, avoltage potential difference is created. The voltage potentialdifference, and hence the voltage, is used to power up control logicthat is positioned within the framework. Ions or current flows from thefirst dissimilar material to the second dissimilar material via thecontrol logic and then through the conducting fluid to complete acircuit. The control logic controls the conductance between the twodissimilar materials and, hence, controls or modulates the conductance.

As the ingestible circuitry is made up of ingestible, and evendigestible, components, the ingestible circuitry results in little, ifany, unwanted side effects, even when employed in chronic situations.Examples of the range of components that may be included are: logicand/or memory elements; effectors; a signal transmission element; and apassive element, such as a resistor or inductor. The one or morecomponents on the surface of the support may be laid out in anyconvenient configuration. Where two or more components are present onthe surface of the solid support, interconnects may be provided. All ofthe components and the support of the ingestible circuitry areingestible, and in certain instances digestible or partially digestible.

In accordance with the various aspects of the present invention, thesystem of the present invention can be located inside specific foodproducts. The system may be co-ingested with food, using on-boardsensing to measure food release into the stomach. Various aspects mayinclude an instrumented container to detect when the system of thepresent invention has been dropped into the container and whether theuser or person ingested the ingestible circuitry. The ingestiblecircuitry may be coated with one or more coatings to protect theingestible circuitry during the mastication process.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows an event indicator system in communication with animplanted device in according to the teaching of the present invention.

FIG. 2A shows the pharmaceutical product of FIG. 1 with the eventindicator system on the exterior of the pharmaceutical product.

FIG. 2B shows the pharmaceutical product of FIG. 1 with the eventindicator system positioned inside the pharmaceutical product.

FIG. 3 is a block diagram representation of one aspect of the eventindicator system with dissimilar metals positioned on opposite ends.

FIG. 4 is a block diagram representation of another aspect of the eventindicator system with dissimilar metals positioned on the same end andseparated by a non-conducting material.

FIG. 5 shows ionic transfer or the current path through a conductingfluid when the event indicator system of FIG. 3 is in contact withconducting liquid and in an active state.

FIG. 5A shows an exploded view of the surface of dissimilar materials ofFIG. 5.

FIG. 5B shows the event indicator system of FIG. 5 with a pH sensorunit.

FIG. 6 is a block diagram illustration of one aspect of the controldevice used in the system of FIGS. 3 and 4.

FIG. 7 is a functional block diagram of a demodulation circuit thatperforms coherent demodulation that may be present in a receiver,according to one aspect.

FIG. 8 illustrates a functional block diagram for a beacon module withina receiver, according to one aspect.

FIG. 9 is a block diagram of the different functional modules that maybe present in a receiver, according to one aspect.

FIG. 10 is a block diagram of a receiver, according to one aspect.

FIG. 11 provides a block diagram of a high frequency signal chain in areceiver, according to one aspect.

FIG. 12 provides a diagram of how a system that includes a signalreceiver and an ingestible event marker may be employed, according toone aspect.

FIG. 13A shows a view of an aspect of an ingestible event marker whichhas a signal amplification element that extends beyond the outer edgesof the upper and lower electrodes (which also serve as signaltransmission elements) to provide a virtual dipole having a length thatis longer than the actual dipole between the signal transmissionelements.

FIG. 13B shows an overhead view of the ingestible event marker of FIG.13A, showing the disc shape of upper electrode and the positioning ofthe upper electrode in the center of disc-shaped signal amplificationelement.

FIG. 13C shows a uniform coating in terms of thickness enveloped aroundan ingestible event marker.

FIG. 13D shows an ingestible event marker that is enveloped in a coatingof non-uniform thickness.

FIG. 13E shows a view of the ingestible event marker identifier coveredon one surface by a coating in the form of a protective cap.

FIG. 13F shows a view where the protective cap from FIG. 13E has beenreplaced by a protective sheet.

FIG. 13G shows a view where a protective cap is pre-affixed to the uppersurface of the ingestible event marker before the ingestible eventmarker is adhered to a tablet carrier.

FIG. 14 shows a system comprising a food product and an ingestible eventmarker packaged separately in a container.

FIG. 15 shows an alternatively system where the food product is packedunder pressure with gas bubbles.

FIG. 16 shows a compound where the ingestible event marker is coatedwith a first coating and a second coating.

FIG. 17 shows a smart package system that includes a zinc air batterythat when opened is activated and sends an electronic signal through thefood product and an ingestible event marker is located inside the foodproduct.

FIG. 18 shows a device comprising a food product provided with a handlecomprising an electrically conductive electrode (shown in section) and abattery located within the handle.

FIG. 19 shows a squeeze tube delivery system may be employed to deliversemi-solid food products and an ingestible event marker packaged in asqueezable tube.

FIG. 20 shows a thin-film drug delivery mechanism that includes a stripthat dissolves when placed in the mouth, e.g., on the tongue.

FIG. 21 shows a system where heat may be applied to the food productbefore it is ingested or detected.

FIG. 22 shows a system 80 for detecting acoustic sounds emitted duringthe mastication process.

DETAILED DESCRIPTION

The present disclosure includes multiple aspects for indicating theoccurrence of an event. As described in more detail below, a system ofthe present invention is used with a conducting fluid to indicate theevent marked by contact between the conducting fluid and the system. Forexample, the system of the present disclosure may be used withpharmaceutical product and the event that is indicated is when theproduct is taken or ingested. The term “ingested” or “ingest” or“ingesting” is understood to mean any introduction of the systeminternal to the body. For example, ingesting includes simply placing thesystem in the mouth all the way to the descending colon. Thus, the termingesting refers to any instant in time when the system is introduced toan environment that contains a conducting fluid. Another example wouldbe a situation when a non-conducting fluid is mixed with a conductingfluid. In such a situation the system would be present in thenon-conduction fluid and when the two fluids are mixed, the system comesinto contact with the conducting fluid and the system is activated. Yetanother example would be the situation when the presence of certainconducting fluids needed to be detected. In such instances, the presenceof the system, which would be activated, within the conducting fluidcould be detected and, hence, the presence of the respective fluid wouldbe detected.

Referring again to the instance where the system is used with theproduct that is ingested by the living organism, when the product thatincludes the system is taken or ingested, the device comes into contactwith the conducting liquid of the body. When the system of the presentinvention comes into contact with the body fluid, a voltage potential iscreated and the system is activated. A portion of the power source isprovided by the device, while another portion of the power source isprovided by the conducting fluid, which is discussed in detail below.

Referring now to FIG. 1, an ingestible capsule 14 that includes a systemof the present invention is shown inside the body. The capsule 14 isconfigured as an orally ingestible pharmaceutical formulation in theform of a pill or capsule. Upon ingestion, the capsule 14 moves to thestomach. Upon reaching the stomach, the capsule 14 is in contact withstomach fluid 18 and undergoes a chemical reaction with the variousmaterials in the stomach fluid 18, such as hydrochloric acid and otherdigestive agents. The system of the present invention is discussed inreference to a pharmaceutical environment. However, the scope of thepresent invention is not limited thereby. The present invention can beused in any environment where a conducting fluid is present or becomespresent through mixing of two or more components that result in aconducting liquid.

Referring now to FIG. 2A, a pharmaceutical product 10, similar to thecapsule 14 of FIG. 1, is shown with a system 12, such as an ingestibleevent marker or an ionic emission module. The scope of the presentinvention is not limited by the shape or type of the product 10. Forexample, it will be clear to one skilled in the art that the product 10can be a capsule, a time-release oral dosage, a tablet, a gel cap, asub-lingual tablet, or any oral dosage product that can be combined withthe system 12.

Additionally, the system 12 of the present invention may be ingestedwithout a pharmaceutical product via a carrier capsule that includesonly the system with no other active agent. In accordance with anotheraspect of the present invention, the system 12 may be used as part of afood product or an ingredient in a food product. For example, the system12 is coated with a protective material as discussed in detail below.The system 12 is then included is the food product similar to anyingredient. Thus, ingestion of that food product may be trackedautomatically, which is often useful in setting where knowing the exactfood take and time of ingestion is needed, for example when a person hasa special diet or is receiving care at a hospital as a patient orin-patient.

In accordance with another example of the present invention, the system12 may be combined with an ingredient commonly used in making food. Forexample, the system 12 may be secured to salt in a manner similar to theway the system 12 is secured to a pharmaceutical product, as discussedbelow. Then as the ingredient with the system 12 is mixed into the food,the food will include the system which will become activated uponingestion.

In accordance with various aspects of the present invention, when thesystem 12 is combined with food and ingested there are variousapproaches to activation of the system 12. In accordance with one aspectof the present invention, the system 12 may be coated with a materialthat breaks and releases the system 12 as the food is being masticated,e.g. chewed or squashed. In accordance with another aspect of thepresent invention, the coating material may be reactive to saliva andwhen in contact with saliva will dissolve or disintegrate and releasethe system 12. Conducting fluids associated with saliva may activate thesystem 12. In accordance with yet another aspect of the presentinvention, the coating material may be reactive to stomach acids anddissolve or disintegrate upon contact with the stomach fluids to releasethe system 12. In accordance with another aspect of the presentinvention, the coating material may be made of material that resistsbreaking or dissolving when masticated or exposed to saliva, such as thebeads found in drinks. In accordance with another aspect of the presentinvention, the coating material may be intentionally destroyed or brokenapart when distributed or mixed in with a food, such as when bread ismixed and prepared for a food (e.g. pizza dough).

Continuing with FIG. 2A, in the shown aspect, the product 10 has thesystem 12 secured to the exterior using known methods of securingmicro-devices to the exterior of pharmaceutical products or aningestible ingredient, for example food or ingredients of food. Exampleof methods for securing the micro-device to the product is disclosed inU.S. Provisional Application No. 61/142,849 filed on Jan. 1, 2009 andentitled HIGH-THROUGHPUT PRODUCTION OF INGESTIBLE EVENT MARKERS as wellas U.S. Provisional Application No. 61/177,611 filed on May 12, 2009 andentitled INGESTIBLE EVENT MARKERS COMPRISING AN IDENTIFIER AND ANINGESTIBLE COMPONENT, the entire disclosure of each is incorporatedherein by reference. Once ingested, the system 12 comes into contactwith body liquids and the system 12 is activated. The system 12 uses thevoltage potential difference to power up and thereafter modulatesconductance to create a unique and identifiable current signature. Uponactivation, the system 12 controls the conductance and, hence, currentflow to produce the current signature.

There are various reasons for delaying the activation of the system 12.In order to delay the activation of the system 12, the system 12 may becoated with a shielding material or protective layer. The layer isdissolved over a period of time, thereby allowing the system 12 to beactivated when the product 10 has reached a target location.

Referring now to FIG. 2B, a pharmaceutical product or an ingestibleproduct/ingredient 20, similar to the capsule 14 of FIG. 1, is shownwith a system 22, such as an ingestible event marker or an identifiableemission module. The scope of the present invention is not limited bythe environment to which the system 22 is introduced. For example, thesystem 22 can be enclosed in a capsule that is taken in additionto/independently from the pharmaceutical product or ingestibleingredient. The capsule may be simply a carrier for the system 22 andmay not contain any product. Furthermore, the scope of the presentinvention is not limited by the shape or type of product 20. Forexample, it will be clear to one skilled in the art that the product 20can be a food product or ingredient, a capsule, a time-release oraldosage, a tablet, a gel capsule, a sub-lingual tablet, or any oraldosage product. In the referenced aspect, the product 20 has the system22 positioned inside or secured to the interior of the product 20. Inone aspect, the system 22 is secured to the interior wall of the product20. When the system 22 is positioned inside a gel capsule, then thecontent of the gel capsule is a non-conducting gel-liquid. On the otherhand, if the content of the gel capsule is a conducting gel-liquid, thenin an alternative aspect, the system 22 is coated with a protectivecover to prevent unwanted activation by the gel capsule content. If thecontent of the capsule is a dry powder or microspheres, then the system22 is positioned or placed within the capsule. If the product 20 is atablet or hard pill, then the system 22 is held in place inside thetablet. Once ingested, the product 20 containing the system 22 isdissolved. The system 22 comes into contact with body liquids and thesystem 22 is activated. Depending on the product 20, the system 22 maybe positioned in either a near-central or near-perimeter positiondepending on the desired activation delay between the time of initialingestion and activation of the system 22. For example, a centralposition for the system 22 means that it will take longer for the system22 to be in contact with the conducting liquid and, hence, it will takelonger for the system 22 to be activated. Therefore, it will take longerfor the occurrence of the event to be detected.

Referring now to FIG. 3, in one aspect, the systems 12 and 22 of FIGS.2A and 2B, respectively, are shown in more detail as system 30. Thesystem 30 can be used in association with any pharmaceutical product, asmentioned above, to determine when a patient takes the pharmaceuticalproduct. As indicated above, the scope of the present invention is notlimited by the environment and the product that is used with the system30. For example, the system 30 may be placed within a capsule and thecapsule is placed within the conducting liquid. The capsule would thendissolve over a period of time and release the system 30 into theconducting liquid. Thus, in one aspect, the capsule would contain thesystem 30 and no product. Such a capsule may then be used in anyenvironment where a conducting liquid is present and with any product.For example, the capsule may be dropped into a container filled with jetfuel, salt water, tomato sauce, motor oil, or any similar product.Additionally, the capsule containing the system 30 may be ingested atthe same time that any pharmaceutical product is ingested in order torecord the occurrence of the event, such as when the product was taken.

In the specific example of the system 30 combined with thepharmaceutical product, as the product or pill is ingested, the system30 is activated. The system 30 controls conductance to produce a uniquecurrent signature that is detected, thereby signifying that thepharmaceutical product has been taken. The system 30 includes aframework 32. The framework 32 is a chassis for the system 30 andmultiple components are attached to, deposited upon, or secured to theframework 32. In this aspect of the system 30, a digestible material 34is physically associated with the framework 32. The material 34 may bechemically deposited on, evaporated onto, secured to, or built-up on theframework all of which may be referred to herein as “deposit” withrespect to the framework 32. The material 34 is deposited on one side ofthe framework 32. The materials of interest that can be used as material34 include, but are not limited to: Cu or CuI. The material 34 isdeposited by physical vapor deposition, electrodeposition, or plasmadeposition, among other protocols. The material 34 may be from about0.05 to about 500 μm thick, such as from about 5 to about 100 μm thick.The shape is controlled by shadow mask deposition, or photolithographyand etching. Additionally, even though only one region is shown fordepositing the material, each system 30 may contain two or moreelectrically unique regions where the material 34 may be deposited, asdesired.

At a different side, which is the opposite side as shown in FIG. 3,another digestible material 36 is deposited, such that materials 34 and36 are dissimilar. Although not shown, the different side selected maybe the side next to the side selected for the material 34. The scope ofthe present invention is not limited by the side selected and the term“different side” can mean any of the multiple sides that are differentfrom the first selected side. Furthermore, even though the shape of thesystem is shown as a square, the shape maybe any geometrically suitableshape. Material 34 and 36 are selected such that they produce a voltagepotential difference when the system 30 is in contact with conductingliquid, such as body fluids. The materials of interest for material 36include, but are not limited to: Mg, Zn, or other electronegativemetals. As indicated above with respect to the material 34, the material36 may be chemically deposited on, evaporated onto, secured to, orbuilt-up on the framework. Also, an adhesion layer may be necessary tohelp the material 36 (as well as material 34 when needed) to adhere tothe framework 32. Typical adhesion layers for the material 36 are Ti,TiW, Cr or similar material. Anode material and the adhesion layer maybe deposited by physical vapor deposition, electrodeposition or plasmadeposition. The material 36 may be from about 0.05 to about 500 μmthick, such as from about 5 to about 100 μm thick. However, the scope ofthe present invention is not limited by the thickness of any of thematerials nor by the type of process used to deposit or secure thematerials to the framework 32.

According to the disclosure set forth, the materials 34 and 36 can beany pair of materials with different electrochemical potentials.Additionally, in the aspects wherein the system 30 is used in-vivo, thematerials 34 and 36 may be vitamins that can be absorbed. Morespecifically, the materials 34 and 36 can be made of any two materialsappropriate for the environment in which the system 30 will beoperating. For example, when used with an ingestible product, thematerials 34 and 36 are any pair of materials with differentelectrochemical potentials that are ingestible. An illustrative exampleincludes the instance when the system 30 is in contact with an ionicsolution, such as stomach acids. Suitable materials are not restrictedto metals, and in certain aspects the paired materials are chosen frommetals and non-metals, e.g., a pair made up of a metal (such as Mg) anda salt (such as CuCl or CuI). With respect to the active electrodematerials, any pairing of substances—metals, salts, or intercalationcompounds—with suitably different electrochemical potentials (voltage)and low interfacial resistance are suitable.

Materials and pairings of interest include, but are not limited to,those reported in Table 1 below. In one aspect, one or both of themetals may be doped with a non-metal, e.g., to enhance the voltagepotential created between the materials as they come into contact with aconducting liquid. Non-metals that may be used as doping agents incertain aspects include, but are not limited to: sulfur, iodine and thelike. In another aspect, the materials are copper iodine (CuI) as theanode and magnesium (Mg) as the cathode. Aspects of the presentinvention use electrode materials that are not harmful to the humanbody.

TABLE 1 Anode Cathode Metals Magnesium, Zinc Sodium, Lithium Iron SaltsCopper salts: iodide, chloride, bromide, sulfate, formate, (other anionspossible) Fe³⁺ salts: e.g. orthophosphate, pyrophosphate, (other anionspossible) Oxygen or Hydrogen ion (H+) on platinum, gold or othercatalytic surfaces Intercalation Graphite with Li, Vanadium oxidecompounds K, Ca, Na, Mg Manganese oxide

Thus, when the system 30 is in contact with the conducting liquid, acurrent path, an example is shown in FIG. 5, is formed through theconducting liquid between material 34 and 36. A control device 38 issecured to the framework 32 and electrically coupled to the materials 34and 36. The control device 38 includes electronic circuitry, for examplecontrol logic that is capable of controlling and altering theconductance between the materials 34 and 36.

The voltage potential created between the materials 34 and 36 providesthe power for operating the system as well as produces the current flowthrough the conducting fluid and the system. In one aspect, the systemoperates in direct current mode. In an alternative aspect, the systemcontrols the direction of the current so that the direction of currentis reversed in a cyclic manner, similar to alternating current. As thesystem reaches the conducting fluid or the electrolyte, where the fluidor electrolyte component is provided by a physiological fluid, e.g.,stomach acid, the path for current flow between the materials 34 and 36is completed external to the system 30; the current path through thesystem 30 is controlled by the control device 38. Completion of thecurrent path allows for the current to flow and in turn a receiver, notshown, can detect the presence of the current and recognize that thesystem 30 has been activate and the desired event is occurring or hasoccurred. Illustrative examples of receivers are shown in FIGS. 7 to 12,as described hereinafter.

In one aspect, the two materials 34 and 36 are similar in function tothe two electrodes needed for a direct current power source, such as abattery. The conducting liquid acts as the electrolyte needed tocomplete the power source. The completed power source described isdefined by the electrochemical reaction between the materials 34 and 36of the system 30 and enabled by the fluids of the body. The completedpower source may be viewed as a power source that exploitselectrochemical conduction in an ionic or a conducting solution such asgastric fluid, blood, or other bodily fluids and some tissues.

Additionally, the environment may be something other than a body and theliquid may be any conducting liquid. For example, the conducting fluidmay be salt water or a metallic based paint.

In certain aspects, these two materials are shielded from thesurrounding environment by an additional layer of material. Accordingly,when the shield is dissolved and the two dissimilar materials areexposed to the target site, a voltage potential is generated.

In certain aspects, the complete power source or supply is one that ismade up of active electrode materials, electrolytes, and inactivematerials, such as current collectors, packaging, etc. The activematerials are any pair of materials with different electrochemicalpotentials. Suitable materials are not restricted to metals, and incertain aspects the paired materials are chosen from metals andnon-metals, e.g., a pair made up of a metal (such as Mg) and a salt(such as CuI). With respect to the active electrode materials, anypairing of substances—metals, salts, or intercalation compounds—withsuitably different electrochemical potentials (voltage) and lowinterfacial resistance are suitable.

A variety of different materials may be employed as the materials thatform the electrodes. In certain aspects, electrode materials are chosento provide for a voltage upon contact with the target physiologicalsite, e.g., the stomach, sufficient to drive the system of theidentifier. In certain aspects, the voltage provided by the electrodematerials upon contact of the metals of the power source with the targetphysiological site is 0.001 V or higher, including 0.01 V or higher,such as 0.1 V or higher, e.g., 0.3 V or higher, including 0.5 volts orhigher, and including 1.0 volts or higher, where in certain aspects, thevoltage ranges from about 0.001 to about 10 volts, such as from about0.01 to about 10 V.

Referring again to FIG. 3, the materials 34 and 36 provide the voltagepotential to activate the control device 38. Once the control device 38is activated or powered up, the control device 38 can alter conductancebetween the materials 34 and 36 in a unique manner. By altering theconductance between materials 34 and 36, the control device 38 iscapable of controlling the magnitude of the current through theconducting liquid that surrounds the system 30. This produces a uniquecurrent signature that can be detected and measured by a receiver (notshown), which can be positioned internal or external to the body.Illustrative examples of receivers are shown in FIGS. 7 to 12, asdescribed hereinafter. In addition to controlling the magnitude of thecurrent path between the materials, non-conducting materials, membrane,or “skirt” are used to increase the “length” of the current path and,hence, act to boost the conductance path, as disclosed in the U.S.patent application Ser. No. 12/238,345 entitled, IN-BODY DEVICE WITHVIRTUAL DIPOLE SIGNAL AMPLIFICATION filed Sep. 25, 2008, the entirecontent of which is incorporated herein by reference. Alternatively,throughout the disclosure herein, the terms “non-conducting material”,“membrane”, and “skirt” are interchangeably with the term “current pathextender” without impacting the scope or the present aspects and theclaims herein. The skirt, shown in portion at 35 and 37, respectively,may be associated with, e.g., secured to, the framework 32. Variousshapes and configurations for the skirt are contemplated as within thescope of the present invention. For example, the system 30 may besurrounded entirely or partially by the skirt and the skirt maybepositioned along a central axis of the system 30 or off-center relativeto a central axis. Thus, the scope of the present invention as claimedherein is not limited by the shape or size of the skirt. Furthermore, inother aspects, the materials 34 and 36 may be separated by one skirtthat is positioned in any defined region between the materials 34 and36.

Referring now to FIG. 4, in another aspect, the systems 12 and 22 ofFIGS. 2A and 2B, respectively, are shown in more detail as system 40.The system 40 includes a framework 42. The framework 42 is similar tothe framework 32 of FIG. 3. In this aspect of the system 40, adigestible or dissolvable material 44 is deposited on a portion of oneside of the framework 42. At a different portion of the same side of theframework 42, another digestible material 46 is deposited, such thatmaterials 44 and 46 are dissimilar. More specifically, material 44 and46 are selected such that they form a voltage potential difference whenin contact with a conducting liquid, such as body fluids. Thus, when thesystem 40 is in contact with and/or partially in contact with theconducting liquid, then a current path, an example is shown in FIG. 5,is formed through the conducting liquid between material 44 and 46. Acontrol device 48 is secured to the framework 42 and electricallycoupled to the materials 44 and 46. The control device 48 includeselectronic circuitry that is capable of controlling part of theconductance path between the materials 44 and 46. The materials 44 and46 are separated by a non-conducting skirt 49. Various examples of theskirt 49 are disclosed in U.S. Provisional Application No. 61/173,511filed on Apr. 28, 2009 and entitled HIGHLY RELIABLE INGESTIBLE EVENTMARKERS AND METHODS OF USING SAME and U.S. Provisional Application No.61/173,564 filed on Apr. 28, 2009 and entitled INGESTIBLE EVENT MARKERSHAVING SIGNAL AMPLIFIERS THAT COMPRISE AN ACTIVE AGENT; as well as U.S.application Ser. No. 12/238,345 filed Sep. 25, 2008 and entitled IN-BODYDEVICE WITH VIRTUAL DIPOLE SIGNAL AMPLIFICATION; the entire disclosureof each is incorporated herein by reference.

Once the control device 48 is activated or powered up, the controldevice 48 can alter conductance between the materials 44 and 46. Thus,the control device 48 is capable of controlling the magnitude of thecurrent through the conducting liquid that surrounds the system 40. Asindicated above with respect to system 30, a unique current signaturethat is associated with the system 40 can be detected by a receiver (notshown) to mark the activation of the system 40. Illustrative examples ofreceivers are shown in FIGS. 7 to 12, as described hereinafter. In orderto increase the “length” of the current path the size of the skirt 49 isaltered. The longer the current path, the easier it may be for thereceiver to detect the current.

Referring now to FIG. 5, the system 30 of FIG. 3 is shown in anactivated state and in contact with conducting liquid. The system 30 isgrounded through ground contact 52. For example, when the system 30 isin contact with a conducting fluid, the conducting fluid provides theground. The system 30 also includes a sensor module 74, which isdescribed in greater detail with respect to FIG. 6. Ion or current paths50 between material 34 to material 36 and through the conducting fluidin contact with the system 30. The voltage potential created between thematerial 34 and 36 is created through chemical reactions betweenmaterials 34/36 and the conducting fluid.

The system 30 also includes a unit 75. The unit 75 includescommunication functions and in accordance with the various aspects ofthe present invention can act as any of the following: a receiver, atransmitter, or a transceiver. Thus, another device that is external tothe system 30, such as a cell phone, an implanted device, a deviceattached to the user's body, or a device placed under the user's skincan communicate with the system 30 through the unit 75. The unit 75 isalso electrically connected to the materials 34 and 36. In accordancewith one aspect of the present invention, any device that is external tothe system 30 may communicate with either the unit 75 or the controlmodule 38 using current flow through the environment surrounding thesystem 30. For example, a patch or receiver that is attached to theuser's body, a cell phone or device being held by the user, or animplanted device, any of which can generate a current signature throughthe user's body. The current signature can include information that isencoded therein. The current signature is detected by the system 30,using the unit 75 or the control module 38, and decoded to allowcommunication to the system 30 from the device external to system 30.Accordingly, the external device can send a signal to the unit 75,either wirelessly or through transconduction, that controls theactivation of the system 30.

If the conditions of the environment change to become favorable tocommunication, as determined by the measurements of the environment,then the unit 75 sends a signal to the control device 38 to alter theconductance between the materials 34 and 36 to allow for communicationusing the current signature of the system 30. Thus, if the system 30 hasbeen deactivated and the impedance of the environment is suitable forcommunication, then the system 30 can be activated again.

Referring now to FIG. 5A, this shows an exploded view of the surface ofthe material 34. In one aspect, the surface of the material 34 is notplanar, but rather an irregular surface. The irregular surface increasesthe surface area of the material and, hence, the area that comes incontact with the conducting fluid. In one aspect, at the surface of thematerial 34, there is an electrochemical reaction between the material34 and the surrounding conducting fluid such that mass is exchanged withthe conducting fluid. The term “mass” as used here includes any ionic ornon-ionic species that may be added or removed from the conductive fluidas part of the electrochemical reactions occurring on material 34. Oneexample includes the instant where the material is CuCl and when incontact with the conducting fluid, CuCl is converted to Cu metal (solid)and Cl— is released into the solution. The flow of positive ions intothe conducting fluid is depicted by the current path 50. Negative ionsflow in the opposite direction. In a similar manner, there is anelectrochemical reaction involving the material 36 that results in ionsreleased or removed from the conducting fluid. In this example, therelease of negative ions at the material 34 and release of positive ionsby the material 36 are related to each other through the current flowthat is controlled by the control device 38. The rate of reaction andhence the ionic emission rate or current, is controlled by the controldevice 38. The control device 38 can increase or decrease the rate ofion flow by altering its internal conductance, which alters theimpedance, and therefore the current flow and reaction rates at thematerials 34 and 36. Through controlling the reaction rates, the system30 can encode information in the ionic flow. Thus, the system 30 encodesinformation using ionic emission or flow.

The control device 38 can vary the duration of ionic flow or currentwhile keeping the current or ionic flow magnitude near constant, similarto when the frequency is modulated and the amplitude is constant. Also,the control device 38 can vary the level of the ionic flow rate or themagnitude of the current flow while keeping the duration near constant.Thus, using various combinations of changes in duration and altering therate or magnitude, the control device 38 encodes information in thecurrent or the ionic flow. For example, the control device 38 may use,but is not limited to any of the following techniques, including BinaryPhase-Shift Keying (PSK), Frequency modulation, Amplitude modulation,on-off keying, and PSK with on-off keying.

As indicated above, the various aspects disclosed herein, such assystems 30 and 40 of FIGS. 3 and 4, respectively, include electroniccomponents as part of the control device 38 or the control device 48.Components that may be present include but are not limited to: logicand/or memory elements, an integrated circuit, an inductor, a resistor,and sensors for measuring various parameters. Each component may besecured to the framework and/or to another component. The components onthe surface of the support may be laid out in any convenientconfiguration. Where two or more components are present on the surfaceof the solid support, interconnects may be provided.

As indicated above, the system, such as control devices 30 and 40,control the conductance between the dissimilar materials and, hence, therate of ionic flow or current. Through altering the conductance in aspecific manner the system is capable of encoding information in theionic flow and the current signature. The ionic flow or the currentsignature is used to uniquely identify the specific system.Additionally, the systems 30 and 40 are capable of producing variousdifferent unique patterns or signatures and, thus, provide additionalinformation. For example, a second current signature based on a secondconductance alteration pattern may be used to provide additionalinformation, which information may be related to the physicalenvironment. To further illustrate, a first current signature may be avery low current state that maintains an oscillator on the chip and asecond current signature may be a current state at least a factor of tenhigher than the current state associated with the first currentsignature.

Referring now to FIG. 6, a block diagram representation of the controldevice 38 is shown. The control device 30 includes a control module 62,a counter or clock 64, and a memory 66. Additionally, the device 38 isshown to include a sensor module 72 as well as the sensor module 74,which was referenced in FIG. 5. The control module 62 has an input 68electrically coupled to the material 34 and an output 70 electricallycoupled to the material 36. The control module 62, the clock 64, thememory 66, and the sensor modules 72/74 also have power inputs (some notshown). The power for each of these components is supplied by thevoltage potential produced by the chemical reaction between materials 34and 36 and the conducting fluid, when the system 30 is in contact withthe conducting fluid. The control module 62 controls the conductancethrough logic that alters the overall impedance of the system 30. Thecontrol module 62 is electrically coupled to the clock 64. The clock 64provides a clock cycle to the control module 62. Based upon theprogrammed characteristics of the control module 62, when a set numberof clock cycles have passed, the control module 62 alters theconductance characteristics between materials 34 and 36. This cycle isrepeated and thereby the control device 38 produces a unique currentsignature characteristic. The control module 62 is also electricallycoupled to the memory 66. Both the clock 64 and the memory 66 arepowered by the voltage potential created between the materials 34 and36.

The control module 62 is also electrically coupled to and incommunication with the sensor modules 72 and 74. In the aspect shown,the sensor module 72 is part of the control device 38 and the sensormodule 74 is a separate component. In alternative aspects, either one ofthe sensor modules 72 and 74 can be used without the other and the scopeof the present invention is not limited by the structural or functionallocation of the sensor modules 72 or 74. Additionally, any component ofthe system 30 may be functionally or structurally moved, combined, orrepositioned without limiting the scope of the present invention asclaimed. Thus, it is possible to have one single structure, for examplea processor, which is designed to perform the functions of all of thefollowing modules: the control module 62, the clock 64, the memory 66,and the sensor module 72 or 74. On the other hand, it is also within thescope of the present invention to have each of these functionalcomponents located in independent structures that are linkedelectrically and able to communicate.

Referring again to FIG. 6, the sensor modules 72 or 74 can include anyof the following sensors: temperature, pressure, pH level, andconductivity. In one aspect, the sensor modules 72 or 74 gatherinformation from the environment and communicate the analog informationto the control module 62. The control module then converts the analoginformation to digital information and the digital information isencoded in the current flow or the rate of the transfer of mass thatproduces the ionic flow. In another aspect, the sensor modules 72 or 74gather information from the environment and convert the analoginformation to digital information and then communicate the digitalinformation to control module 62. In the aspect shown in FIG. 5, thesensor modules 74 is shown as being electrically coupled to the material34 and 36 as well as the control device 38. In another aspect, as shownin FIG. 6, the sensor module 74 is electrically coupled to the controldevice 38 at connection 78. The connection 78 acts as both a source forpower supply to the sensor module 74 and a communication channel betweenthe sensor module 74 and the control device 38.

Referring now to FIG. 5B, the system 30 includes a pH sensor module 76connected to a material 39, which is selected in accordance with thespecific type of sensing function being performed. The pH sensor module76 is also connected to the control device 38. The material 39 iselectrically isolated from the material 34 by a non-conductive barrier55. In one aspect, the material 39 is platinum. In operation, the pHsensor module 76 uses the voltage potential difference between thematerials 34/36. The pH sensor module 76 measures the voltage potentialdifference between the material 34 and the material 39 and records thatvalue for later comparison. The pH sensor module 76 also measures thevoltage potential difference between the material 39 and the material 36and records that value for later comparison. The pH sensor module 76calculates the pH level of the surrounding environment using the voltagepotential values. The pH sensor module 76 provides that information tothe control device 38. The control device 38 varies the rate of thetransfer of mass that produces the ionic transfer and the current flowto encode the information relevant to the pH level in the ionictransfer, which can be detected by a receiver (not shown). Illustrativeexamples of receivers are shown in FIGS. 7 to 12, as describedhereinafter. Thus, the system 30 can determine and provide theinformation related to the pH level to a source external to theenvironment.

As indicated above, the control device 38 can be programmed in advanceto output a pre-defined current signature. In another aspect, the systemcan include a receiver system that can receive programming informationwhen the system is activated. In another aspect, not shown, the switch64 and the memory 66 can be combined into one device.

In addition to the above components, the system 30 may also include oneor other electronic components. Electrical components of interestinclude, but are not limited to: additional logic and/or memoryelements, e.g., in the form of an integrated circuit; a power regulationdevice, e.g., battery, fuel cell or capacitor; a sensor, a stimulator,etc.; a signal transmission element, e.g., in the form of an antenna,electrode, coil, etc.; a passive element, e.g., an inductor, resistor,etc.

In certain aspects, the ingestible circuitry includes a coating layer.The purpose of this coating layer can vary, e.g., to protect thecircuitry, the chip and/or the battery, or any components duringprocessing, during storage, or even during ingestion. In such instances,a coating on top of the circuitry may be included. Also of interest arecoatings that are designed to protect the ingestible circuitry duringstorage, but dissolve immediately during use. For example, coatings thatdissolve upon contact with an aqueous fluid, e.g. stomach fluid, or theconducting fluid as referenced above. Also of interest are protectiveprocessing coatings that are employed to allow the use of processingsteps that would otherwise damage certain components of the device. Forexample, in aspects where a chip with dissimilar material deposited onthe top and bottom is produced, the product needs to be diced. However,the dicing process can scratch off the dissimilar material, and alsothere might be liquid involved which would cause the dissimilarmaterials to discharge or dissolve. In such instances, a protectivecoating on the materials prevents mechanical or liquid contact with thecomponent during processing can be employed. Another purpose of thedissolvable coatings may be to delay activation of the device. Forexample, the coating that sits on the dissimilar material and takes acertain period of time, e.g., five minutes, to dissolve upon contactwith stomach fluid may be employed. The coating can also be anenvironmentally sensitive coating, e.g., a temperature or pH sensitivecoating, or other chemically sensitive coating that provides fordissolution in a controlled fashion and allows one to activate thedevice when desired. Coatings that survive the stomach but dissolve inthe intestine are also of interest, e.g., where one desires to delayactivation until the device leaves the stomach. An example of such acoating is a polymer that is insoluble at low pH, but becomes soluble ata higher pH. Also of interest are pharmaceutical formulation protectivecoatings, e.g., a gel cap liquid protective coating that prevents thecircuit from being activated by liquid of the gel cap.

Identifiers of interest include two dissimilar electrochemicalmaterials, which act similar to the electrodes (e.g., anode and cathode)of a power source. The reference to an electrode or anode or cathode areused here merely as illustrative examples. The scope of the presentinvention is not limited by the label used and includes the aspectwherein the voltage potential is created between two dissimilarmaterials. Thus, when reference is made to an electrode, anode, orcathode it is intended as a reference to a voltage potential createdbetween two dissimilar materials.

When the materials are exposed and come into contact with the bodyfluid, such as stomach acid or other types of fluid (either alone or incombination with a dried conductive medium precursor), a potentialdifference, that is, a voltage, is generated between the electrodes as aresult of the respective oxidation and reduction reactions incurred tothe two electrode materials. A voltaic cell, or battery, can thereby beproduced. Accordingly, in aspects of the invention, such power suppliesare configured such that when the two dissimilar materials are exposedto the target site, e.g., the stomach, the digestive tract, etc., avoltage is generated.

In certain aspects, one or both of the metals may be doped with anon-metal, e.g., to enhance the voltage output of the battery.Non-metals that may be used as doping agents in certain aspects include,but are not limited to: sulfur, iodine and the like.

In accordance with the various aspects of the present invention, thesystem of the present invention can be inside specific food products(e.g. a granola bar), with one of the data encoded and communicated bythe system being the caloric content of the food or other relevantdietary information, e.g. fiber sugar content, fat type and content etc.This may help people on a diet monitor their daily intakes, getincentives for staying on-diet, etc. Also, the system is co-ingestedwith food, using on-board sensing to measure food release into thestomach, e.g. fat content. Various aspects may include an instrumentedcup that detects when the system of the present invention has beendropped into the cup and whether the user or person took a drink(similar, for example, to the inhaler product described in PCTApplication Ser. No. PCT/US11/31986, filed Apr. 11, 2011, the entiredisclosure of which is incorporated herein by reference), and how muchthey drank. An advantage of this aspect of the present invention is thatit may be useful for people who take regular supplements in the form ofa powder or other, which is mixed with water before drinking.

In accordance with other aspects of the present invention, chemicalmarkers can incorporate certain marker species into the food (e.g. salt,low-or-high pH, protein, and lipid). When ingested, a marker species isreleased into stomach environment. With the sensing capability, thesystem of the present invention can detect chemical-binding receptors onthe surface or by coating on the system that reacts with achemically-active coating (e.g. a coating such as aspecific-ion-conducting glass membrane that allows only the desiredmarker species to penetrate). In various aspects, the ingestible deviceis co-ingested with the food, and may be used, among other things, tomeasure/detect the presence of the “marker species”. The system that isingestible and masticable can contain a detector capable of measuringendocanabinoids, as described for example, in the publication byDiPatrizio et al. entitled, “Endocannabinoid signal in the gut controlsdietary fat intake”, for example reference, the entire disclose of whichis incorporated herein by reference). When the signal is detected—e.g.,a sign that high fat food intake has occurred—the user or patient isinstructed via phone message or other communication to take aprescription (also RIS-enabled) to disrupt the endocannabinoid signal,thus reducing the craving for more high fat foods.

In accordance with another aspect of the present invention, the systemis detectable when the skirt is missing. In accordance with anotheraspect of the present invention, the system is safe to bite, for exampleby thinning the silicon. In accordance with another aspect of thepresent invention, several of the systems of the present invention areplaced in the food so that if some of the ingestible devices are damagedduring mastication there are still functional devices left. Thus, thesystems could be distributed throughout the food, so that the number ofsystems detected gives an indication of the quantity of food consumed.Additionally, another aspect of the present invention teaches that thesystem of the present invention can be surrounded with gummy materialand laminated between polymer layers that are soluble at low pH, but notin neutral pH (saliva). Furthermore, by reversing the coating, theopposite effect is achieved in accordance with another aspect of thepresent invention. First coat/laminate the system of the presentinvention with a pH sensitive polymer and then insert it inside small,gummy particles, e.g., gummy bites, to help survive in the mouth. Thus,the system of the present invention is inside a gummy-bear likeprotective layer, and may be reduced in size, such as skirt-less orflexible skirt. The protective layer may consist of multilayers or mayhave a density or solubility gradient such that the material nearest thesystem is only slowly soluble and likely to be swallowed due to slipperysurface, rounded shape and very small size. The system, according toanother aspect of the present invention, would have a circuitmodification that, in addition to probing the local impedance, has afeedback to postpone activation while the local impedance is high. Thisallows time for the remaining layer(s) to dissolve. The system isactivated or turns on as soon as liquid penetrates through, but cannotsend sufficient signal strength for detection, the high current andbattery layer depletion is postponed until the impedance dropssufficiently. Thus, the system according to this aspect of the presentinvention, for example, is put into pre-measured meal and snack types toread out what was consumed.

For purposes of illustration, various receivers may be used with variousaspects of the present invention. In one example of a receiver,sometimes referred to herein as a “signal receiver”, two or moredifferent demodulation protocols may be employed to decode a givenreceived signal. In some instances, both a coherent demodulationprotocol and a differential coherent demodulation protocol may beemployed. FIG. 7 provides a functional block diagram of how a receivermay implement a coherent demodulation protocol, according to one aspectof the invention. It should be noted that only a portion of the receiveris shown in FIG. 7. FIG. 7 illustrates the process of mixing the signaldown to baseband once the carrier frequency (and carrier signal mixeddown to carrier offset) is determined. A carrier signal 2221 is mixedwith a second carrier signal 2222 at mixer 2223. A narrow low-passfilter 2220 is applied of appropriate bandwidth to reduce the effect ofout-of-bound noise. Demodulation occurs at functional blocks 2225 inaccordance with the coherent demodulation scheme of the presentinvention. The unwrapped phase 2230 of the complex signal is determined.An optional third mixer stage, in which the phase evolution is used toestimate the frequency differential between the calculated and realcarrier frequency can be applied. The structure of the packet is thenleveraged to determine the beginning of the coding region of the BPSKsignal at block 2240. Mainly, the presence of the sync header, whichappears as an FM porch in the amplitude signal of the complexdemodulated signal is used to determine the starting bounds of thepacket. Once the starting point of the packet is determined the signalis rotated at block 2250 on the IQ plane and standard bit identificationand eventually decoded at block 2260.

In addition to demodulation, the transbody communication module mayinclude a forward error correction module, which module providesadditional gain to combat interference from other unwanted signals andnoise. Forward error correction functional modules of interest includethose described in PCT Application Serial No. PCT/US2007/024225 andpublished as WO 2008/063626, the disclosure of which is hereinincorporated by reference. In some instances, the forward errorcorrection module may employ any convenient protocol, such asReed-Solomon, Golay, Hamming, BCH, and Turbo protocols to identify andcorrect (within bounds) decoding errors.

In another example, the receiver includes a beacon module as shown inthe functional block diagram of FIG. 8. The scheme outlined in FIG. 8outlines one technique for identifying a valid beacon. The incomingsignal 2360 represents the signals received by electrodes, bandpassfiltered (such as from 10 KHz to 34 KHz) by a high frequency signalingchain (which encompasses the carrier frequency), and converted fromanalog to digital. The signal 2360 is then decimated at block 2361 andmixed at the nominal drive frequency (such as, 12.5 KHz, 20 KHz, etc.)at mixer 2362. The resulting signal is decimated at block 2364 andlow-pass filtered (such as 5 KHz BW) at block 2365 to produce thecarrier signal mixed down to carrier offset—signal 2369. Signal 2369 isfurther processed by blocks 2367 (fast Fourier transform and thendetection of two strongest peaks) to provide the true carrier frequencysignal 2368. This protocol allows for accurate determination of thecarrier frequency of the transmitted beacon.

FIG. 9 provides a block functional diagram of an integrated circuitcomponent of a signal receiver according to an aspect of the invention.In FIG. 9, receiver 2700 includes electrode input 2710. Electricallycoupled to the electrode input 2710 are transbody conductivecommunication module 2720 and physiological sensing module 2730. In oneaspect, transbody conductive communication module 2720 is implemented asa high frequency (HF) signal chain and physiological sensing module 2730is implemented as a low frequency (LF) signal chain. Also shown are CMOStemperature sensing module 2740 (for detecting ambient temperature) anda 3-axis accelerometer 2750. Receiver 2700 also includes a processingengine 2760 (for example, a microcontroller and digital signalprocessor), non-volatile memory 2770 (for data storage) and wirelesscommunication module 2780 (for data transmission to another device, forexample in a data upload action).

FIG. 10 provides a more detailed block diagram of a circuit configuredto implement the block functional diagram of the receiver depicted inFIG. 9, according to one aspect of the invention. In FIG. 10, receiver2800 includes electrodes e1, e2 and e3 (2811, 2812 and 2813) which, forexample, receive the conductively transmitted signals by an IEM and/orsense physiological parameters or biomarkers of interest. The signalsreceived by the electrodes 2811, 2812, and 2813 are multiplexed bymultiplexer 2820 which is electrically coupled to the electrodes.

Multiplexer 2820 is electrically coupled to both high band pass filter2830 and low band pass filter 2840. The high and low frequency signalchains provide for programmable gain to cover the desired level orrange. In this specific aspect, high band pass filter 2830 passesfrequencies in the 10 KHz to 34 KHz band while filtering out noise fromout-of-band frequencies. This high frequency band may vary, and mayinclude, for example, a range of 3 KHz to 300 KHz. The passingfrequencies are then amplified by amplifier 2832 before being convertedinto a digital signal by converter 2834 for input into high powerprocessor 2880 (shown as a DSP) which is electrically coupled to thehigh frequency signal chain.

Low band pass filter 2840 is shown passing lower frequencies in therange of 0.5 Hz to 150 Hz while filtering out out-of-band frequencies.The frequency band may vary, and may include, for example, frequenciesless than 300 Hz, such as less than 200 Hz, including less than 150 Hz.The passing frequency signals are amplified by amplifier 2842. Alsoshown is accelerometer 2850 electrically coupled to second multiplexer2860. Multiplexer 2860 multiplexes the signals from the accelerometerwith the amplified signals from amplifier 2842. The multiplexed signalsare then converted to digital signals by converter 2864 which is alsoelectrically coupled to low power processor 2870.

In one aspect, a digital accelerometer (such as one manufactured byAnalog Devices), may be implemented in place of accelerometer 2850.Various advantages may be achieved by using a digital accelerometer. Forexample, because the signals the digital accelerometer would producesignals already in digital format, the digital accelerometer couldbypass converter 2864 and electrically couple to the low powermicrocontroller 2870—in which case multiplexer 2860 would no longer berequired. Also, the digital signal may be configured to turn itself onwhen detecting motion, further conserving power. In addition, continuousstep counting may be implemented. The digital accelerometer may includea FIFO buffer to help control the flow of data sent to the low powerprocessor 2870. For instance, data may be buffered in the FIFO untilfull, at which time the processor may be triggered to turn awaken froman idle state and receive the data.

Low power processor 2870 may be, for example, an MSP430 microcontrollerfrom Texas Instruments. Low power processor 2870 of receiver 2800maintains the idle state, which as stated earlier, requires minimalcurrent draw—e.g., 10 μA or less, or 1 μA or less.

High power processor 2880 may be, for example, a VC5509 digital signalprocess from Texas Instruments. The high power processor 2880 performsthe signal processing actions during the active state. These actions, asstated earlier, require larger amounts of current than the idlestate—e.g., currents of 30 μA or more, such as 50 μA or more—and mayinclude, for example, actions such as scanning for conductivelytransmitted signals, processing conductively transmitted signals whenreceived, obtaining and/or processing physiological data, etc.

Also shown in FIG. 10 is flash memory 2890 electrically coupled to highpower processor 2880. In one aspect, flash memory 2890 may beelectrically coupled to low power processor 2870, which may provide forbetter power efficiency.

Wireless communication element 2895 is shown electrically coupled tohigh power processor 2880 and may include, for example, a BLUETOOTH™wireless communication transceiver. In one aspect, wirelesscommunication element 2895 is electrically coupled to high powerprocessor 2880. In another aspect, wireless communication element 2895is electrically coupled to high power processor 2880 and low powerprocessor 2870. Furthermore, wireless communication element 2895 may beimplemented to have its own power supply so that it may be turned on andoff independently from other components of the receiver—e.g., by amicroprocessor.

With an idle state in mind, the following paragraphs provide exampleconfigurations of receiver components shown in FIG. 10 during variousstates of the receiver, according to one aspect of the invention. Itshould be understood that alternative configurations may be implementeddepending on the desired application.

In an idle state, for example, the receiver draws minimal current.Receiver 2800 is configured such that low power processor 2870 is in aninactive state (such as idle state) and high power processor 2880 is inan inactive state (such as idle state), and circuit blocks related toperipheral circuitry and their power supplies required during variousactive states remain off (for example, wireless communication module2895 and the analog front end). For example, the low power processor mayhave a 32 KHz oscillator active and may consume a few μA current orless, including 0.5 μA or less. In the idle state, the low powerprocessor 2870 may, for example, wait for a signal to transfer to anactive state. The signal might be external such as an interrupt orinternally generated by one of the device's peripherals, such as atimer. During the high power processors idle state, the high powerprocessor may, for example, be running off a 32 KHz watch crystal. Thehigh power processor may, for example, wait for a signal to transfer toactive state.

When the receiver is in the sniff state, low power processor 2870 is inan idle state and high power processor 2880 is in an idle state. Inaddition, the circuit blocks relating to the analog front end includingA/D converter that is needed for the sniff function are on (in otherwords, the high frequency signal chain). As stated earlier, the beaconsignal module may implement various types of sniff signals to achievelow power efficiency.

Upon detection of a transmitted signal, a higher power demodulate anddecode state may be entered. When the receiver is in the demodulate anddecode state, low power processor 2870 is in an active state and highpower processor 2880 is in an active state. High power processor 2880may, for example, be running from a 12 MHz or near crystal oscillatorwith a PLL-based clock multiplier giving the device a 108 MHz clockspeed. The low power processor 2870 may, for example, run off aninternal R-C oscillator in the range of 1 MHz to 20 MHz and consumepower in the range of 250 to 300 μA per MHz clock speed during activestates. The active state allows for processing and any transmissionsthat may follow. Required transmissions may trigger the wirelesscommunication module to cycle from off to on.

When the receiver is in collect ECG and accelerometer state, the circuitblocks relating to the accelerometer and/or ECG signal conditioningchain are on. The high power processor 2880 is in an in idle stateduring collection, and in an active state (for example, running from a12 MHz or near crystal oscillator with a PLL-based clock multipliergiving the device a 108 MHz clock speed) during processing andtransmission. The low power processor 2870 is in an active state duringthis state and may run off an internal R-C oscillator in the range of 1MHz to 20 MHz and consume power in the range of 250 to 300 uA per MHzclock speed.

The low power processor (e.g., MSP shown in FIG. 10) and high powerprocessor (e.g., DSP shown in FIG. 10) may communicate with each otherusing any convenient communication protocol. In some instances, thesetwo elements, when present, communicate with each via a serialperipheral interface bus (hereinafter “SPI bus”). The followingdescription describes the signaling and messaging scheme implemented toallow the high power processor and low power processor to communicateand send messages back and forth along the SPI bus. For the followingdescription of the communication between the processors, “LPP” and “HPP”are used in place of “low power processor” and “high power processor”,respectively, to stay consistent with FIG. 10. The discussion, however,may apply to other processors than those shown in FIG. 10.

FIG. 11 provides a view of a block diagram of hardware in a receiveraccording to an aspect of the invention related to the high frequencysignal chain. In FIG. 11, receiver 2900 includes receiver probes (forexample in the form of electrodes 2911, 2912 and 2913) electricallycoupled to multiplexer 2920. Also shown are high pass filter 2930 andlow pass filter 2940 to provide for a band pass filter which eliminatesany out-of-band frequencies. In the aspect shown, a band pass of 10 KHzto 34 KHz is provided to pass carrier signals falling within thefrequency band. Example carrier frequencies may include, but are notlimited to, 12.5 KHz and 20 KHz. One or more carriers may be present. Inaddition, receiver 2900 includes analog to digital converter 2950—forexample, sampling at 500 KHz. The digital signal can thereafter beprocessed by the DSP. Shown in this aspect is DMA to DSP unit 2960 whichsends the digital signal to dedicated memory for the DSP. The directmemory access provides the benefit of allowing the rest of the DSP toremain in a low power mode.

An example of a system that includes a receiver is shown in FIG. 12. InFIG. 12, system 3500 includes a pharmaceutical composition 3510 thatcomprises an ingestible device such as an ingestible event marker,“IEM.” Also present in system 3500 is signal receiver 3520. Signalreceiver 3520 is configured to detect a signal emitted from theidentifier of the IEM 3510. Signal receiver 3520 also includesphysiologic sensing capability, such as ECG and movement sensingcapability. Signal receiver 3520 is configured to transmit data to apatient's an external device or PDA 3530 (such as a smart phone or otherwireless communication enabled device), which in turn transmits the datato a server 3540. Server 3540 may be configured as desired, e.g., toprovide for patient directed permissions. For example, server 3540 maybe configured to allow a family caregiver 3550 to participate in thepatient's therapeutic regimen, e.g., via an interface (such as a webinterface) that allows the family caregiver 3550 to monitor alerts andtrends generated by the server 3540, and provide support back to thepatient, as indicated by arrow 3560. The server 3540 may also beconfigured to provide responses directly to the patient, e.g., in theform of patient alerts, patient incentives, etc., as indicated by arrow3565 which are relayed to the patient via PDA 3530. Server 3540 may alsointeract with a health care professional (e.g., RN, physician) 3555,which can use data processing algorithms to obtain measures of patienthealth and compliance, e.g., wellness index summaries, alerts,cross-patient benchmarks, etc., and provide informed clinicalcommunication and support back to the patient, as indicated by arrow3580.

In one aspect the ingestible event marker is combined with food and/orfood and pharmaceuticals in several different configurations where theingestible event marker can survive the mastication, i.e., chewing,process. The following description provides several combinations ofingestible event marker with food and/or food and pharmaceuticals inmany different forms.

In one aspect, the ingestible event marker and associated electroniccomponents retain their functional integrity from the time it reachesits destination while being masticated and still remains operable.Alternative, other aspects are disclosed where the ingestible eventmarker does not necessarily survive the mastication process, however,mastication or other bodily sounds are detected by way of acousticsensing techniques. Applications of any of these aspects include,without limitation, pediatric, elderly, veterinary, nutricitical,acoustic feedback effect, among others. The types of food combinationsinclude without limitation solid, semi-solid, and liquid forms of foodsand discussed with more particularity hereinbelow. The combination ofingestible event marker and food or the combination of ingestible eventmarker, food, and pharmaceutical may be coated with substances orcompounds to preserve the integrity of the ingestible event marker untilsuch time as the food product is prepared for consumption, consumedorally by mastication or otherwise, or the food product has beenconsumed orally and the ingestible event marker is passing through thegastrointestinal system where the coating is configured to dissolve inthe esophagus, stomach, small intestine, large intestine, colon, orotherwise. These and various alternatives, aspects, and embodiments ofcombinations of ingestible event marker and food products andcombinations of ingestible event marker, food products, andpharmaceuticals are now described.

It is a familiar occurrence for people who take medicine to crush themedicine and mix it with a food product such as applesauce, pudding,peanut butter, candy, among others, to make ingestion of the medicinemore palatable. This is particularly common with infants, children,elderly, and even pets. For example, the medicine may be located ininfant formula, mixed with applesauce for their children, pudding forthe elderly, and peanut butter for the pet dog. Thus, people are used tomixing food products with pharmaceutical drugs, prescription orotherwise, nutritional supplements, or otherwise, to facilitate theprocess of adherence to a particular regimen.

Thus in pediatric applications, the medicines or supplements may bemixed or otherwise combined with baby formula and/or smart feedingbottle, since formula is likely the only type of food a lot of babieseat during infancy. For children, the medicine can be mixed or otherwisecombined with candy or semisoft foods such as gelatin, applesauce,pudding, powder drinks, sports drinks, chewable vitamins or supplements.For the elderly, the medicine can be mixed or otherwise combined withsoft foods or liquids, including, for example, pudding, powdered energydrinks, dietary supplements, among others. For veterinary applications,the medicine may be mixed or otherwise combined with animal feed.

In each of the above listed applications, an ingestible event markerwould be combined with a food product and/or combined with the foodproduct and a pharmaceutical product. In addition to the aboveapplications, other applications of interest include systems that couldsurvive in an aqueous formulation and activate upon mastication orexposure to digestive enzymes. Such ingestible event markers would becontained in a protective capsule, coating, or bubble such that alongwith an oral suspension of fluid or nutritional supplement the user alsoingests an ingestible event marker device which provide a signal wheningested. Thus the ingestible event marker and food or supplement may bepackaged and stored in a moist environment and protected until it iseither chewed or located in the stomach or both. It will be appreciatedthat most food products or substances that can be used or prepared foruse as food and medicine is that a lot of foods are going to have somemoisture content in them. The moisture content in the food has to bemanaged to prevent the ingestible event marker from activatingprematurely. Exceptions would include freeze dried food products. Theobjective is to keep the ingestible event marker dry, free from moistureor liquid, until it is masticated and ready to emit.

An example of an ingestible event marker of interest is depicted inFIGS. 13A and 13B. The ingestible event marker shown in FIGS. 13A and13B includes an integrated circuit component as well as upper and lowerelectrodes, where the upper and lower electrodes are configured suchthat upon contact with stomach fluid current runs through the integratedcircuit to cause one or more functional blocks in the circuit to emit adetectable signal. The marker shown in FIGS. 13A and 13B includes avirtual dipole signal amplification element, as reviewed in greaterdetail in PCT application serial no. PCT/US2008/077753, the disclosureof which is herein incorporated by reference.

FIG. 13A provides a view of an aspect of an ingestible event marker 110which has a signal amplification element that extends beyond the outeredges of the upper and lower electrodes (which also serve as signaltransmission elements) to provide a virtual dipole having a length thatis longer than the actual dipole between the signal transmissionelements. As shown in FIG. 13A, ingestible event marker 110 includesintegrated circuit component 112, having an upper electrode 114 and alower electrode 116 (which may comprise two distinct material layers).Also shown is disc-shaped signal amplification element or non-conductivecurrent path extender (“skirt”) 118.

FIG. 13B provides an overhead view of the ingestible event marker 110 ofFIG. 13A, showing the disc shape of upper electrode 114 and thepositioning of the upper electrode in the center of disc-shaped signalamplification element 118. The distance that the edge of the signalamplification element may extend beyond the edge of electrodes may vary,and in certain instances is 0.05 mm or more, e.g., 0.1 mm or more,including 1.0 mm or more, such as 5.0 mm or more and including 10 mm ormore, where the distance may not exceed 100 mm in some instances.

As can be seen in the aspect depicted in FIGS. 13A to 13B, the upper andlower electrodes are planar electrodes, where these electrodes may haveany convenient shape, such as square, disc, triangular, oval, irregular,etc. The disc-shaped signal amplification element 118 is a planar discstructure, where the edge of the signal amplification element extendsbeyond the edge of the planar upper and lower electrodes. In thedepicted ingestible event marker 110, the radius of the signalamplification element is longer than the radius of the upper and lowerelectrodes, for example by 1 mm or more, such as by 10 mm or more.

Ingestible event markers produced may be configured in a variety ofdifferent formats. Formats of interest include, but are not limited to,tablets and capsules.

The ingestible event marker 110 may include a coating, which coating maycover one or more surfaces of the ingestible event marker 110 or all ofthe surfaces of the ingestible event marker, such that the ingestibleevent marker is enveloped by the coating. The protection function of thecoating can vary. For example, the coating can be configured to protectthe ingestible event marker or components thereof, such as theintegrated circuit component, the electrode components, etc., duringprocessing, during storage, or even during various phase of ingestion,e.g., esophagus, stomach, small intestine, large intestine, colon. Forinstance, one may not desire the circuitry to be exposed to the bodyfluids or activating electrically conductive fluids after the ingestibleevent marker is ingested. In such instances, it may be desirable to onlyhave the incomplete battery and transmit antennas be exposed toelectrically conductive fluids, with the rest of the circuitry beingprotected. In such instances, a coating on top of the circuitrycomponent that is ingestible but does not dissolve until the device hasfinished its signal transmission may be provided.

Also of interest are coatings that are designed to protect theingestible circuitry component during storage, but that dissolveimmediately during use. For example, coatings that dissolve upon contactwith an aqueous fluid, such as stomach fluid or fluids commonly found infood products, may be employed. Also of interest are protective coatingsthat are employed to allow the use of processing the ingestible eventmarker with a food product or food product/pharmaceutical compound thatwould otherwise damage certain components of the device. In suchinstances, a protective coating on the ingestible event marker thatprevents mechanical or liquid contact with the ingestible event markercan be employed. Coatings of interest include pliable coatings thatprotect the ingestible event marker from forces that may be experiencedby during ingestible event marker storage prior to ingestion orcombining with food products containing moisture content, such asapplesauce, pudding, energy drinks and the like. Coatings of interestalso include environmentally sensitive coatings, such as pH sensitivecoatings that protect the ingestible event marker from a liquid presentin a capsule but then dissolve once the ingestible event marker contactsstomach fluid. Examples of such coatings are liquid protective coatingsthat prevent the circuit component of the ingestible event marker frombeing activated by liquid of the carrier component of the ingestibleevent marker. Another purpose of the coatings may be to control theactivation of the device. For example, an edible coating that covers theelectrodes and takes a certain period of time, e.g., five minutes, todissolve upon contact with stomach fluid may be employed. The coatingcan also be an environmentally sensitive coating, e.g., a temperature orpH sensitive coating, or other chemically sensitive coating thatprovides for dissolution in a controlled fashion and allows one toactivate the device when desired. Coatings that survive the stomach butdissolve in the intestine are also of interest, e.g., where one desiresto delay activation until the device leaves the stomach. An example ofsuch a coating is a polymer that is insoluble at low pH, but becomessoluble at a higher pH. Coatings of interest further include hot-meltcoatings and sugar coatings.

Of interest in certain instances are hydrogel coatings. Hydrogelcoatings are polymeric coatings made up of one or more different typesof non-water soluble polymers, where the coatings absorb water uponcontact with an aqueous medium to produce a hydrated gel-structure thathas a high water content, such as 90% or more w/w, including 95% or morew/w, such as 99% or more w/w.

Any physiologically acceptable hydrogel composition may be employed as acoating, where hydrogel compositions of interest may include one or moreof the following polymers: polyethylene oxides, acetates, etc. In thehydrated gel structure state, the coating may be pliable, and therebyprotect the ingestible event marker during processing. In someinstances, the hydrogel coating may include one or more agents whichprovide for a controlled environment (for example in terms ofconductivity) when the ingestible event marker reaches the targetphysiological site. Agents of interest include, but are not limited to:salts of physiologically acceptable electrolytes, such as but notlimited to: sodium ion, chloride ion, potassium ion and calcium ion,magnesium ion, etc. Specific physiologically compatible salts ofinterest include, but are not limited to: KCl, NaCl, MgCl2, and thelike.

Coatings may take a variety of different configurations, such as layers,snap-fit pre-made capsule components, etc. When present, coatings maycover only a portion of the ingestible event marker or envelope theentire. The coating may be uniform in terms of thickness. An example ofan ingestible event marker that is enveloped in a coating of uniformthickness is shown in FIG. 13C. In FIG. 13C, ingestible event marker 120includes integrated circuit component 112, having an upper electrode 114(which may comprise two distinct material layers) and a lower electrode116, as well disc-shaped signal amplification element 118. Also shown isuniform coating 122.

Alternatively, the coating may be non-uniform, e.g., where the coatingis thicker towards the center of the ingestible event marker as opposedto the edges of the ingestible event marker. An example of an ingestibleevent marker that is enveloped in a coating of non-uniform thickness isshown in FIG. 13D. In FIG. 13D, ingestible event marker 130 includesintegrated circuit component 112, having an upper electrode 114 (whichmay comprise two distinct material layers) and a lower electrode 116, aswell disc-shaped signal amplification element 118. Also shown isnon-uniform coating 132, which non-uniform coating 132 is thicker aboveand below the electrode components 114 and 116 and thinner towards theouter edge of the signal amplification element 118.

In some instances, the coating covers only a portion of the ingestibleevent marker. FIG. 13E provides a view of the ingestible event markeridentifier 140 covered on one surface by a coating in the form of aprotective cap 142. Also shown in FIG. 13E is carrier 144 in the form ofa tablet, where the carrier 144 together with the ingestible eventmarker identifier 140 and protective cap 142 make up an ingestible eventmarker 146. FIG. 13G shows a variation of an ingestible event marker 160according to the present invention. Ingestible event marker 160 is madeup of integrated circuit component 112, upper and lower electrodes 114and 116 and signal amplification element 118. In the view shown in FIG.13G, protective cap 162 is pre-affixed to the upper surface of theingestible event marker before the ingestible event marker is adhered toa tablet carrier. In an alternative configuration shown in FIG. 13F,protective cap 142 from FIG. 13E has been replaced by protective sheet148. Where desired, the protective sheet 148 may fit with the uppersurface 147 of a tablet component 145 to be level with the upper surface147 of the tablet component 145. The tablet component 145 may define acavity (not shown) for receiving the ingestible event marker 140 suchthat when the protective sheet 148 is fitted into the cavity it isapproximately level with the upper surface 147.

Any coating associated with an ingestible event marker may be opaque inorder to prevent the end-user from seeing the ingestible event markerassociated with carrier of the ingestible event marker. Alternatively,the coating may be transparent so as to provide ready visualization ofthe ingestible event marker that is stably associated with the carrier.

With respect to fabrication of such coatings, the coatings may beassociated with the ingestible event marker using any convenientprotocol, such as by use of a fluidized bed, deposition as well asinstances where the coating is pre-made and then fit over the ingestibleevent marker, such as a cap that is glued onto a portion of theingestible event marker or capsule components that are press-fit onto acomposite structure of an ingestible event marker and a carrier, such asa tablet. In some instances, an assembly unit may be configured toassociate a coating with the ingestible event marker, such as bydispensing a precursor coating fluid onto an ingestible event marker,where the precursor coating fluid cures into the desired coating.

In one aspect, the ingestible event marker may be coated with an agentthat burst when it gets wet. In one aspect, the ingestible event markermay be encased by a wax coating. Chewing the food product breaks up thewax coating releasing the ingestible event marker in the mouth. The waxcoating may be applied by dipping the ingestible event marker in waxsuch that it is formed around the ingestible event marker. The waxcoating provides moisture protection and would prevent the ingestibleevent marker from activating prematurely because the wax is impermeableto water. Food grade waxes provide suitable permeability to moisture. Insome aspects, a synthetic wax with a melting point below bodytemperature may be employed. In other aspects, waxes with very sharpmelting points that would ride up body temperature may be employed. Inanother aspect, a swellable hydrogel layer may be provided underneaththe wax layer to break it up. This may be accomplished with meltingwaxes. Sodium bicarbonate may be added to the hydrogel to assist it tobreak up the wax layer.

In another aspect, the ingestible event marker may be encased incongealed grease. Like wax coatings, congealed grease coatings wouldprovide a certain level of impermeability to moisture to prevent theingestible event maker from activating prematurely.

In other aspects, refrigerated, environmentally controlled, or maximumexposure types of food products including nutritional products thatcannot survive in the back of a hot semi-trailer truck may be coated toprevent the ingestible event marker for activating prematurely.

In various aspects, the ingestible event marker is provided with acoating to enable the ingestible event to better survive crushing by theteeth during mastication. Even with the disclosed coatings, not allingestible event markers may survive mastication, thus a plurality ofingestible event markers may be distributed within the coating material.In one aspect, the ingestible event marker may be coated with agelatin-like coating to protect the ingestible event marker from beingcrushed when chewed. Likewise, the gelatin-like coating protects theteeth from biting down directly onto the ingestible event marker. Othercoatings include rubber-elastic candy based on a starch matrix. Examplesof some of these coatings are known in industry as gummy bear typecoatings. A gummy bear material, e.g., a gelation, may be formulated inmany different flavors such as Tapioca, for example.

In one aspect, the medicines may be mixed with or otherwise combinedwith a semisoft high moisture content food product such as applesauce,for example. The ingestible event marker would comprise a protectivecoating and then be mixed in with the food product and medicine at thetime scheduled for administering the medicinal dose.

Ingredients for films and coatings used in the food and pharmaceuticalindustries can provide protective and other selectively functionalcoatings over the ingestible sensor. Hydrocolloids such as cellulosederivatives (HPC, HPMC are examples), carrageenan, sodium alginate,pectin may be used in protective edible coatings of the ingestiblesensor. The films may be cast or extruded, sprayed over the sensor, orthe sensor immersed in the coating material. Multiple films may be used.Several examples are provided.

In a preferred embodiment a bilayer comprising an HPC based adhesivelayer and a sodium alginate based protection layer are cast andlaminated together prior to attachment over the sensor. The films maycomprise plasticizers and adhesive and film forming additions. Examplesinclude tri-ethyl cellulose, glycerin, polyvinylpyrrolidone.

FIG. 14 shows a system 200 comprising a food product 202 and aningestible event marker 204 packaged separately in a container 206. Inaspect, the food product 202, let's assume applesauce, is packed in avacuum 208 and the ingestible event marker 204 is packed in a lid 210 ofthe container 206. When the lid 210 of the package 206 is opened, theingestible event marker 204 and the food product 202 are exposed to fullatmospheric pressure and the ingestible event marker 204 is releasedinto the food product 202, where it can be mixed together with themedicine. Although the medicine may be included in the package 206, forflexibility, the medicine may be added after the container 206 isopened.

In one aspect, an opening is formed when the vacuum pack 206 is releasedthe in process of opening it and the ingestible event marker 204 isreleased 212 into the food product 202. The ingestible event marker 204would have a longer shelf life because it is combined with the foodproduct 202 when the food is ready to be eaten. Once in the food, theingestible event marker 204 can last 10-30 minutes. Once mixed into thefood product 202, the coating provided around the ingestible eventmarker 204 protects the ingestible event marker 204 from dissolving inthe food product 202 to preserve battery power. Ideally, dissolution ofthe ingestible event marker 204 should not begin until it reaches thestomach. In case the coating dissolves while the ingestible event marker204 is still in the food product 202, a soft start routine may beemployed to postponed a full power up of the ingestible event marker 204to prevent expending all the current of the partial power source batterywhile the ingestible event marker 204 is still in the food product 202.The battery is consumed with the high current as the circuit is closed(activated). Nevertheless, once the ingestible event marker 204 becomeswet, the battery will be eventually be consumed in about 10 minutes toabout 30 minutes, thus providing adequate time for the food product 202to be eaten.

In one aspect the medicine in combination with the food product 202 canbe made chewable. Also, to determined how much of the food product isconsumed, multiple ingestible event markers 204 can be distributedthrough out the food product 202, for example, 100 ingestible eventmarkers 204 may be located within a popsicle and the number ofingestible event markers 204 that are activated provides an indicationof the quantity of medicine that was ingested. For example, if 100ingestible event markers 204 are evenly distributed in the food product202 and if 30 ingestible event markers 204 are activated, then it can beconcluded that 30% of the medicine was ingested. A similar distributioncan be done with a caramel log such as a Tootsie roll.

Hydrochloride materials may be utilized as coatings around theingestible event marker 204 to control water absorption by theingestible event marker 204 to and hence control the activation time ofthe ingestible event marker 204. Materials comprising alginic acid knownas alginates are considered hydrochloride materials. An alginic acid,also called algin or alginate, is an anionic polysaccharide distributedwidely in the cell walls of brown algae, where through binding withwater it forms a viscous gum. In extracted form it absorbs waterquickly; it is capable of absorbing 200-300 times its own weight inwater. Accordingly, alginate materials can be utilized as a coatingmaterial to control the activation of ingestible event markers 204 bycontrolling moisture access to the ingestible event marker 204.

In one aspect, materials with pH driven triggers can be used in thecoating surrounding the ingestible event marker 204 to determine howmuch material dissolved and to drive delivery. The coating on theingestible event marker 204 is pH sensitive to change the permittivityof moisture relative to the pH of the fluid in which the coating, andhence the ingestible event marker 204, is in contact in. In a high pHenvironment, the coating is impermeable and enables very little moistureto penetrate the ingestible event marker 204. In a low pH environment,the coating is porous and enables more moisture to penetrate to theingestible event marker 204.

Enteric coatings, which are designed to dissolve in the intestine alsomay be provided around the ingestible event marker 204 to controlactivation thereof. An enteric coating is porous in a neutral pHenvironment and impermeable in a low pH environment. For example, thestomach is acidic with a pH of 3 or below, which is typically very low.An enteric coating provided on the ingestible event marker 204 willprevent it from dissolving, and thus activating, until it reaches anenvironment with a more neutral pH such as the intestine. It would bedesirable to confirm good detection of the ingestible event marker 204in the intestine. An enteric coating can be applied to the ingestibleevent marker 204 to delay dissolution and activation until it reachesthe intestine. The enteric coating could be utilized in conjunction witha family of pharmaceuticals where all of the absorption occurs in theintestine. The enteric coating would provide a measure of control to getall of the pharmaceutical absorbed in the intestine. Accordingly, theenteric coating prevents the pharmaceutical dose form (tablet, capsule,etc.) from dissolving in the stomach. Rather, it dissolves when it getsinto a neutral pH in the intestine. Thus, utilizing enteric coatings maybe very useful for incorporating this into like sodas, because youalways have a little bit of citric acid in there which will keep the pHrelatively low.

In one aspect, one or more ingestible event markers 204 can be added tothe package 206 or the food products 202. In one aspect, one or moreingestible event markers 204 can be added to food products 202 prior tocooking. The coating may be configured to dissolve when it reaches acertain temperature, at which point the ingestible event marker 204becomes soluble and is irreversibly activated. A few ingestible eventmarkers 204 with heat sensitive coatings can be added to food products,such as hamburgers. As long as the hamburger remains frozen it remainsinert, however, as but as the hamburger is grilled to a particulartemperature the coating dissolves in the heat and the ingestible eventmarker 204 now is in a soluble state. Accordingly, when the hamburger iseaten, the ingestible event marker 204 begins communicating.

In another aspect, two separate materials may be utilized to coat theingestible event marker 204. The materials can be located on top of eachother either at room temperature or while frozen. The materials can beconfigured to not react all until they are heated up to grillingtemperature and then they react and the ingestible event marker isirreversibly turned on. The materials may have different thermalexpansion coefficients. Accordingly, two materials with differentexpansion coefficients layered on top of each other will curl up whenthey heat up. The medicine may be set in a powder, like hot chocolate,and then the hot water is added. Adding the medicine in the hot wateractivates this device, and then it changes state. The different thermalcoefficients also may work with polymers that are very temperaturesensitive and can provide a double layer of protection. The grillingconfiguration could be applied in food safety and may be tailored toemit a signal at the temperature when the food has been safely cooked.

The ingestible event marker 204 could be located in the marshmallows orsomething like that. So as the child is drinking hot chocolate heswallows the ingestible event marker that has been activated in themicrowave oven. Marshmallows dissolve away.

Thermal electric marshmallows can be utilized to power up the ingestibleevent marker 204. Then the marshmallows can be put into the hotchocolate or as they float on the surface, a thermal differential can beobtained.

In one aspect, the medicine may be embedded in a semi soft moist foodproduct 202, such as peanut butter, and the ingestible event 204 markermay be embedded in a hard dry food product, such as a graham cracker.The two components can be combined just before they are eaten. So byadding the two components the user will receive the ingestible eventmarker 204 by swallowing. The ingestible event marker 204 is alreadybasically activated. This may be considered one aspect of a hybriddelivery system with the food product in one chamber and the ingestibleevent marker is in another chamber. When you chew on the hybrid package,the chamber is crushed and the divider and the ingestible event marker204 activates in the mouth.

FIG. 15 shows an alternatively system 201 where the food product 202 ispacked under pressure 213 with gas bubbles. When the pressure 213 isreleased by opening the lid 211, bubbles activate the ingestible eventmarker 204 in a chemically inert flow path. When the bubbles arestrained through the fluid, the high pressure inert flow path releasesthe ingestible event marker 204 into the food product 202. The liquidand the gas liquid phases provide suitable pressure to release theingestible event marker 204. As the lid 211 of the container 215 isopened like a can of soda the ingestible event marker 202 containingpackage 216 explodes and releases 217 the ingestible event marker 204into the food product 202. The release 217 of the ingestible eventmarker 204 would be automatic upon opening the package 215.

In one aspect, the ingestible event marker 204 is packaged in therelease package 216 in a cold environment so that it is frozen and thenencapsulated into a relaxed bladder, like a balloon, under pressure. Thepressure would tend to keep the moisture out of the release package 216containing the ingestible event marker 204. The packaging of themedicine or the food with the medicine in it also may be done at thefreezing point (zero centigrade) to keep everything frozen. The liquidlayer, a frozen flow inert layer that may be coated with a wax layer, islocated in the food product 202 (e.g., applesauce), and sealed off. Oncesealed off, the food product 202 is coated with a wax layer and can bestored at room temperature under very high pressure so it is balancedwhen the container is opened to release the outer pressure. Once thefood product 202 (e.g., applesauce) and the medicine is mixed in, theingestible event marker 204 is released into the mixture to determinewhen the combination of food product 202 and medicine is ingested.

In another aspect the medicine may be packaged separately from the foodproduct 202, e.g., just like granola is packaged separately from yogurtto prevent it from getting soggy. This would allow the food product 202to be packaged separately from the medicine such that different medicineor a different brand of the same medicine can be given with the foodproduct 202.

It may be more practical to enable a pressure package 216 rather than avacuum package 206. In a pressure package 216, liquid is used topressurize the container. A flow inert known as CF_(X), CHF_(X), orC_(X)F_(Y) is employed as the pressure source. The boiling point and thefreezing point of the CF_(X), CHF_(X), or C_(X)F_(Y) is based on thelength of the carbon chain. The longer the carbon chain the easier itcan be frozen at room temperature. This technique can be used with avariety of food products 202.

FIG. 16 shows a compound 218 where the ingestible event marker 204 iscoated with a first coating 220 and a second coating 222. In one aspect,the first coating 220 may be a chocolate coating and the second coating222 may be a polymeric coating. The ingestible event marker 204 can belocated within the first coating 220 and packaged and prepared with thefirst coating 220 at a temperature within a narrow range. For example,if the ingestible event marker 204 is part of a chocolate first coating220 and the chocolate is beyond its melting point, the ingestible eventmarker 204 cannot be used. Accordingly, the first coating 220 can beused to control the temperature at which the ingestible event marker 204activates. The first coating 220 and the ingestible event marker 204compound can then be coated with a polymeric type second coating 222that has a sharp melting point. The compound 218 can be a two-pieceassembly where an outer layer formed by the second coating 222 may bemade of sugar to provide moisture resistance and an inner layer formedby the first coating 220 provides resistance and cushioning to toleratethe mastication process. The inner layer 220 material may be coatedaround the ingestible event marker 204 to provide cushion duringmastication and to enable the ingestible event marker 204 to beswallowed without damaging the ingestible event marker 204 or damagingthe teeth. The various layers of the masticable could be adjusted. Forexample, multi-layers may be provided in the masticable such that outerlayers provide a slippery and chewy feeling and inners layers that aremore protective.

FIG. 17 shows a smart package system 230 that includes a zinc airbattery and RFID circuit 238 that when opened is activated and sends anelectronic signal 224 through the food product 202 (e.g., applesauce)and an ingestible event marker 204 is located inside the food product202. In one aspect, it may involve peeling something like peeling thelid 226 off the smart package system 230 container 231 and the rest isautomatic. The lid 226, or other component of the smart package system230 container 231, comprises a battery and RFID circuit 238 embeddedinto it. Battery contacts are activated when the lid 226 is opened suchthat just opening the lid 226 up activates the battery and RFID circuit238. The ingestible event marker 204 comprises a coating 232 that isimpervious to water to protect the ingestible event marker 204 from thefood product 202. The coating 232 can be broken or destroyed to releasethe ingestible event marker 204 when it receives the electronic signal.The ingestible event marker 204 comprises a detection circuit 234 thatreceives the electronic signal 224 by RFID coupling and the electronicmessage to the ingestible event marker 204 causes the coating 232 tobreak up and release the ingestible event marker 204. The breakingprocess may be electrically controlled. In one aspect, the detectioncircuit 234 of the ingestible event marker 204 includes an electronicRFID interface that, upon receiving a certain message, causes theingestible event marker 204 to break up the surrounding coating 232material by driving a an electric current trough it. The material 232may be configured to break open as it heats up when the electric currentis driven through it, thus influencing the environment and causing thecoating 232 shell to burst. The signal is generated only when the lid226 of the smart package 231 is opened and thus, the ingestible eventmarker 204 is activated only upon opening the lid 226 of the smartpackage 230.

A special receiver may be utilized with pediatric users to communicatewith the ingestible event markers 204. In one aspect, the specialreceiver directly talks to the ingestible event markers 204 withdestructible coatings 232, and periodically sends out information. Afteringestion, the ingestible event marker 204 stays in its shell until itreceives a signal from the special receiver. When the signal isreceived, the destructible coating is broken and the ingestible eventmarker 204 is released into the stomach. If the destructible coating isimpervious to water, the ingestible event marker 204 can be placed intoany liquid. The destructible signal may be an RF signal transmitted bythe receiver.

In one aspect, an electrical signal stronger than what can be generatedby a receiver is generated by a wall unit plugged into a household ACpower outlet. The electrical signal from the home hub plugs into thewall and broadcasts a really strong signal to break open the coating 232when the ingestible event marker in the stomach. Silicon dioxide toseparate capacitive plates may provide two-orders of magnitudes ofgreater coupling of energy during the wireless interrogation, which isseven microns now.

The detection circuit 234 may capture power with a resonant circuitdriving a diode and scrubbing heat off to cause the flow of polymers inthe coating 232 to melt and release the ingestible event marker 204. Inother words, the smart package 230 communicates with the ingestibleevent marker 204 with RF signals, resonance, or electrochemical reactionto make the coating 232 material boil and break open the shell thatcontains the ingestible event marker 204 and release the ingestibleevent marker 204 into the food product 202. Once the ingestible eventmarker 204 is released into the food product 202 (e.g., applesauce) theingestible event marker 204 communicates for about 15 minutes. Thepurpose ultimately is to provide adherence information and make iteasier to take medicine. When the food product 202 smart package 230contains moisture or something in a water environment, the anodecatheter should be protected from getting wet. Ideally like animpervious coating 232 shell that is broken. It is easier to takemedication with adherence information on it.

In one aspect, the coating 232 may be a gelatin like coating (gummybear) that may be soft, hard, or a gradient between soft and hard. Agradient would be is desirable such that the outside comprises aslippery and chewy layer and the inside comprises a more protectivelayer and small enough for the critical dimension to make it easy toswallow. The inner layer could be electrically conductive once it getswet or masticated. It could be a gelatin layer in a polymer matrix suchthat when it is chewed or swallowed, the gelatin leeches out to provideelectrically conductive pathways to generate a signal that can bedetected by a receiver as well as the ingestible event marker 204located in the food product 202. It could be either a conductive signalor it could be a Bluetooth signal, or some other short range wirelesssignal. When the smart package 230 is opened, a signal is sent in theform of an audible sound so that you know that you have five minutes toingest the food product 202 containing the ingestible event marker 204.This is akin to the five minutes to self-destruct countdown popular insci-fi movies, like the Aliens.

In various aspects, the food products may be selected among a group offoods that are eaten by children and/or the elderly. The applicationsfor the elderly are similar to those for pediatric applications in thatthe system is making it easier for them to take their medicine. The foodproduct may be a fruit flavored gelatin known under the trade nameJell-O or caramel logs known under the trade name Tootsie Roll.

Coatings to protect the ingestible circuitry during the masticationprocess include, for example, hydrocolloids such as cellulosederivatives (HPC, HPMC are examples), carrageenan, sodium alginate,pectin may be used in protective edible coatings of the ingestiblesensor.

Other coatings may comprise sugars, starches, gelatin, and pectin may beprocessed to produce a soft masticable coating that could be bitten downon while protecting the sensor circuitry inside. Multiple layers of suchcoatings may be used to provide a gradient of stiffness through thecoating, such that the inner layers are made stiffer and more protectiveand the outer layers are softer and more chewable.

The outer layers, with or without additional coatings, may be formulatedto produce a smooth and slippery outer surface during mastication toenhance swallowing of the sensor.

FIG. 18 shows a device 240 comprising a food product 202 provided with ahandle 242 comprising an electrically conductive electrode 241 (shown insection) and a battery 244 located within the handle 242. The device 240is turned on by the battery 244 when the packaging is removed from thefood product 202 at which time an ingestible event marker 204 emitselectrically conductive signal through the handle 242 and to the user'sbody. Every time the food product 202 (e.g., lollipop) is licked itgenerates an electrically conductive signal that can be detected by apatch receiver. In one aspect, the conductive metal handle comprises anelectrical conductor such as a metal electrode to electrically couple tothe hand and as the lollipop is licked. In another aspect a quantifiedliquid that is different from body fluid goes through the mouth throughthe quantified liquid delivery. The signal encodes how much of themedication is in the lollipop.

Other techniques that can be used with children include aerosols,inhalation or nasal aerosol to spray them in nasal cavity, sodas,juices, smart popsicles. A smart popsicle is frozen and activates as itbegins to melt. The popsicle can stay frozen which keeps the shell coldand it will stay frozen. It might give us a little more range for thelax. The drug is can be in the popsicle or it's being done while thedrug is taken.

Coatings which break and expose the sensor when masticated may comprise,for example, film coatings based on sugars and starches includingamylopectin, potato starch, maltodextrin, or cellulose, may bemanufactured as thin coatings or films which will fracture whenmasticated. These may be used in combination with pH dependent coatings.

Coatings with solubility controlled in the mouth, esophagus, stomach maycomprise, for example, coatings containing materials with pH dependentsolubility may be used as functional coatings over the ingestion sensor.Reverse enteric coatings may be used for dissolution of the coating inthe stomach to expose the sensor after mastication or after swallowing.Examples are aminoalkyl methacrylate copolymers and other acrylic basedcoatings.

FIG. 19 shows a squeeze tube delivery system 250 may be employed todeliver semi-solid food products 202 and an ingestible event marker 204packaged in a flexible container such as a squeezable tube 252. The tube252 is squeezed by compressing and breaking or rupturing a wall 254separating the ingestible event marker 204 from the food product 202.Much like hand warmers that are activated by breaking and releasing twoor more compounds that generate heat when mixed. The tube 252 could beactivated by twisting and breaking open the wall 254. Otherwise, theingestible event marker 204 may comprise a coating 256 that can bebroken by twisting the tube 252 to release the ingestible event marker204 and then by pressurizing the tube 252 to break the wall 254 andcombining the ingestible event marker 204 with food product 202 as it issqueezed from the tube 252. The food product 202 may be liquid, suchthat the combination food product 202 and ingestible event marker 204can be drunk after the tube is twisted to break the wall 254. Theprocess of getting the food 202 out also activates the ingestible eventmarkers 204 contained in the tube 252. In one aspect, this technique maybe applied to a juice box and/or applesauce container, to dispense gellike foods where the container is squeezed to get the gel out, amongothers.

In another aspect, small beads may be located in a drink and when theyare bitten, they break open and activate. This may be an alternative tochomping the ingestible event marker 204 directly to protect the teeth.

In another aspect, the semi-solid food product packaged in thesqueezable plastic tube 252 may include a restriction and the semi-solidfood product and ingestible event markers 204 are squeezed out past therestriction. Several semi-solid food products can be contained in thesqueezable plastic tube to mix the different foods when the tube issqueezed. For example, one compartment may contain peanut butter andanother compartment may contain chocolate such that they are mixed uponsqueezing the tube so both food products can be dispensed from the tube.

The same technology described above for children and the elderly can beutilized with animal food and animal feed. The animal would have areceiver or a collar for detecting the ingestible event marker 204signal. A receiver could be added to a GPS tracking collar or a taggingcollar that may already be worn by the animal. A bucket transmits asignal when the food is gone by detecting the absence of food. When theanimals are feeding from the bucket, the system communicates with theirpatch. Antibiotics can be located in the bucket and the feed bucket doesthe communicating. In cases where we only want to know what theconsumption is. You've got a number of animals, for example, to identifythe animals that actually showed up at the trough.

FIG. 20 shows a thin-film drug delivery mechanism 260 that includes astrip 262 that dissolves when placed in the mouth, e.g., on the tongue.The thin-film drug delivery system 260 employs a dissolving film 262 ororal drug strip to administer drugs via absorption in the mouth(buccally or sublingually) and/or via the small intestines(enterically). Orally disintegrating tablet or orodispersible tablet(ODT) is a drug dosage form available for a limited range ofover-the-counter (OTC) and prescription medications. ODTs differ fromtraditional tablets in that they are designed to be dissolved on orunder the tongue rather than swallowed whole. The film 262 can beprepared using hydrophilic polymers that rapidly dissolve on the tongueor buccal cavity, delivering the drug to the systemic circulation viadissolution when contact with liquid is made. Ingestible event markers204 could be incorporated into the dissolvable thin-film 262 deliverysystem to delivery an ingestible event marker 204 in conjunction withthe pharmaceutical. Once the thin-film 262 dissolves, the ingestibleevent marker 204 enters the mouth and is simply swallowed. Theingestible event marker 204 also could be coated with a chewable gelatincoating 264 to prevent chomping on the ingestible event marker. Theingestible event marker 204 could be coated to survive being embedded inthe dissolvable strip and to get wet and activate when it is placed inthe mouth.

The ingestible event markers can be located in food products consumed byelite athletes in training. Accordingly, the ingestible event markerscan be located into an energy bar, sports drink, and the like. Theingestible event marker can be used for tracking consumption of suchfood products. Digital nutriceutical may be provided for the convenienceof using food as a delivery method for a pharmaceutical.

Other suitable food products for combining with ingestible event markersis the jelly bean, baby food, lip balm to go over the lips slowly toapply the balm on the lips and then eventually eat it along withingestible event marker and does not require chewing. Along with lipbalms, ingestible event markers 204 can be combined with medicatedsalves and things that are rubbed on the skin.

FIG. 21 shows a system 270 where heat may be applied to the food product202 before it is ingested or detected. The heat source 272 may be amicrowave oven, for example. Although the food product 202 is notnecessarily heated by the microwave oven, a coating component 274 thatincludes the ingestible event marker 204 heats up and bursts open torelease the ingestible event marker. For example, the food product 202can be placed in the microwave for ˜3 seconds and the ingestible eventmarker 204 bursts from its coating shell 274 so that it can be eaten ordrunk. A microwave oven 272 heats food by bombarding it withelectromagnetic radiation in the microwave spectrum causing polarizedmolecules in the food to rotate and build up thermal energy in a processknown as dielectric heating. Microwave ovens heat foods quickly andefficiently because excitation is fairly uniform in the outer 25-38 mmof a dense (high water content) food item; food is more evenly heatedthroughout (except in thick, dense objects) than generally occurs inother cooking techniques. The electromagnetic radiation of microwaveovens is substantially tuned to excite water molecules. Once thematerial forming the coating shell 274 absorbs a predetermined amount ofradiation, it bursts to release the ingestible event marker 204.

Thus, an ingestible event marker 204 can be encapsulated by a shell 274of a material that absorbs microwave radiation tuned for watermolecules. The ingestible event marker 204 may include the shell 274around it to prevent it from dissolving and activating in the foodproduct. The shell 274 may include a material that is tuned to microwaveradiation so that it gets hot and explodes to cause the shell 274 toburst in a nominal amount of time and release the ingestible eventmarker into the food product. Once the ingestible event marker 204 isexposed to the food product 202 (e.g., applesauce, peanut butter, babyfood, and the like) the ingestible event marker 204 begins theactivation process. Further, the drug or pharmaceutical can be disbursedinto the food product in a similar manner at the same time theingestible event marker 204 is released.

Alternatively, the pharmaceutical may be contained in the food product202 as a new formulation or combination of food and drug which may begeneric otherwise but now it is in the food product (e.g., applesauce,peanut butter, baby food, and the like).

In yet another alternative, of the drug delivery technique, theingestible event marker 204 and the medication are both located in aburstable capsule 274 that absorbs microwave energy. The burstablecapsule 274 is dropped in the food product ands then placed in themicrowave oven 272 for a few seconds until the capsule bursts and themedication and ingestible event marker are stirred and eaten.

Alternatively, the ingestible event marker 204 encapsulating material274 can be developed to absorb microwave radiation tuned for moleculesother than water. Still in another alternative, a circuit can be tunedto absorb the microwave radiation and the circuit can be used as anenergy pickup to generate enough heat to disrupt the ingestible eventmarker 204 encapsulating or coating material 274 to release theingestible event marker 204. Thus, properly tuned, the ingestible eventmarker 204 could be released from the encapsulating material in a shortamount of time, such as, for example, about one second.

FIG. 22 shows a system 280 for detecting acoustic sounds 282 emittedduring the mastication process. The current challenge is having enoughpower to dissolve the ingestible event marker 204 to communicate aparticular problem.

Thus, mastication itself can be an act which generates energy. Becauseanything being masticated naturally goes inside the mouth, instead oflocating a receiver patch 284 on the patient's waist, a receiver patch284 can be located between the ear 286 and the jaw 288 to sensemastication utilizing the movements of the jaw 288. The receiver patch284 can be placed on the ear 286 or behind the ear to render invisiblefrom the front, or may be located on glasses. This technique may besuitable for utilizing on obese people when mastication is detected.

In one aspect, a piezoelectric element 290 can be activated duringmastication without the need for a chemical reaction to power up theingestible event marker 204. Thus, during the mastication process, thepiezoelectric element 290 emits an electric signal at a specificfrequency that doesn't mix with all the other or acoustic mechanicalsound to hear the acoustic sound. When the piezoelectric element 290 isdeformed during the mastication process it develops an electric voltagepotential, which can be coupled to a capacitor and charge the capacitor.The capacitor could remain charged with the voltage until the ingestibleevent marker reaches the stomach and then broadcast the encoded signalfor a short duration. The receiver patch 284 may be a simple relativelysmall form factor acoustic microphone, which can be an off the shelfintegrated circuit placed against the skin. Alternatively, the acousticreceiver can be located in a headphone. Thus a completely passivemicrophone based acoustic detection system can detect the unique soundmade while masticating.

In yet another aspect, a system is configured to detect acoustic soundsemitted when the ingestible event marker 204 is destroyed or partiallydestroyed during the mastication process. In one aspect, an audiblenoise created by the destruction of the ingestible event marker 204 orthe destruction of an envelope that covers the ingestible event marker204 can be monitored by a device. The device may be worn inside, behind,or outside the ear or as an attachment to glasses or hearing aid (sothat it is not obviously visible) so that it is proximate to the mouthwhere the crushing happens and the audible signal evolves which maypreferably be communicated conductively and by other means as well.

The audible signal may be captured from the mouth, vocal cord, and othernoises such as hissing noises made by the elderly, breathingdifficulties, wheezing noise, frequent hiccups, moans and otherbody-generated noises, as well.

Alternatively, in one aspect a mobile device could be employed as asensor platform where passive sensing functionality can be implementedwith a mobile device and link into the health system platform. Thepassive sensing functionality include motion, location, and interactionanalysis with mobile device features.

In Alzheimer's, dementia, and broader neurodegenerative diseases it isdesirable to determine how medication adherence can slow diseaseprogression. In addition, in areas like Parkinson's metrics may bedesirable to support the lowest possible dose and dosing frequencyrelative to effect in order to preserve efficacy in a particularindividual.

In one aspect, the microphone in the mobile device may be utilized topassively capture and record calls by a neurodegenerative patient. Vocalstrength and tone changes are keys in neurodegenerative diseaseprogression.

The phone-recorded vocal patterns and changes in voice strength and tonewould be analyzed to grade changes and associate these with diseaseprogression and stage. This information could be then be combined withadherence sensing as well as physical markers of activity, gate, andsleep patterns to create treatment scores and indexes.

It is to be understood that this invention is not limited to particularaspects or aspects described, as such may vary. It is also to beunderstood that the terminology used herein is for the purpose ofdescribing particular aspects only, and is not intended to be limiting,since the scope of the present invention will be limited only by theappended claims.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range, is encompassed within the invention. The upper and lowerlimits of these smaller ranges may independently be included in thesmaller ranges and are also encompassed within the invention, subject toany specifically excluded limit in the stated range. Where the statedrange includes one or both of the limits, ranges excluding either orboth of those included limits are also included in the invention.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although any methods andmaterials similar or equivalent to those described herein can also beused in the practice or testing of the present invention, representativeillustrative methods and materials are now described.

All publications and patents cited in this specification are hereinincorporated by reference as if each individual publication or patentwere specifically and individually indicated to be incorporated byreference and are incorporated herein by reference to disclose anddescribe the methods and/or materials in connection with which thepublications are cited. The citation of any publication is for itsdisclosure prior to the filing date and should not be construed as anadmission that the present invention is not entitled to antedate suchpublication by virtue of prior invention. Further, the dates ofpublication provided may be different from the actual publication dateswhich may need to be independently confirmed.

It is noted that, as used herein and in the appended claims, thesingular forms “a”, “an”, and “the” include plural referents unless thecontext clearly dictates otherwise. It is further noted that the claimsmay be drafted to exclude any optional element. As such, this statementis intended to serve as antecedent basis for use of such exclusiveterminology as “solely,” “only” and the like in connection with therecitation of claim elements, or use of a “negative” limitation.

It will be appreciated that as used herein, the term “dissolve” may beused to indicate melt, soften, liquefy, thaw, disrupt, break up, breakopen, break apart, or otherwise destroy a layer or coating of materialencapsulating an ingestible event marker either wholly or partially torelease the ingestible event marker.

As will be apparent to those of skill in the art upon reading thisdisclosure, each of the individual aspects described and illustratedherein has discrete components and features which may be readilyseparated from or combined with the features of any of the other severalaspects without departing from the scope or spirit of the presentinvention. Any recited method can be carried out in the order of eventsrecited or in any other order which is logically possible.

Although the foregoing invention has been described in some detail byway of illustration and example for purposes of clarity ofunderstanding, it is readily apparent to those of ordinary skill in theart in light of the teachings of this invention that certain changes andmodifications may be made thereto without departing from the spirit orscope of the appended claims.

Accordingly, the preceding merely illustrates the principles of theinvention. It will be appreciated that those skilled in the art will beable to devise various arrangements which, although not explicitlydescribed or shown herein, embody the principles of the invention andare included within its spirit and scope. Furthermore, all examples andconditional language recited herein are principally intended to aid thereader in understanding the principles of the invention and the conceptscontributed by the inventors to furthering the art, and are to beconstrued as being without limitation to such specifically recitedexamples and conditions. Moreover, all statements herein recitingprinciples, aspects, and aspects of the invention as well as specificexamples thereof, are intended to encompass both structural andfunctional equivalents thereof. Additionally, it is intended that suchequivalents include both currently known equivalents and equivalentsdeveloped in the future, i.e., any elements developed that perform thesame function, regardless of structure. The scope of the presentinvention, therefore, is not intended to be limited to the exemplaryaspects shown and described herein. Rather, the scope and spirit ofpresent invention is embodied by the appended claims.

What is claimed is:
 1. An apparatus, comprising: a food product; atleast one ingestible device associated with the food product tocommunicate information, the ingestible device associated with aningestible medication to be ingested in conjunction with the foodproduct; and at least one coating material surrounding the at least oneingestible device; wherein the coating is configured to release the atleast one ingestible device upon the occurrence of an event.
 2. Theapparatus of claim 1, wherein the event comprises combining the foodproduct and the at least one ingestible device.
 3. The apparatus ofclaim 1, wherein the at least one ingestible device is stored within thefood product and the event comprises mastication of the food product,wherein the coating is configured to release the ingestible deviceduring mastication of the food product.
 4. The apparatus of claim 1,further comprising a container to contain the food product and the atleast one ingestible device separately within the container.
 5. Theapparatus of claim 4, wherein the food product is vacuum packed and theat least one ingestible device is releasably attached to the containerand is releasable into the food product upon opening of the container torelease the vacuum.
 6. The apparatus of claim 4, wherein the foodproduct is pressure packed and the at least one ingestible device isreleasably attached to the container and is releasable into the foodproduct upon opening of the container to release the pressure.
 7. Theapparatus of claim 4, wherein the coating material is configured torelease the at least one ingestible device into the food product.
 8. Theapparatus of claim 4, wherein the coating material is configured torelease the at least one ingestible device during mastication.
 9. Theapparatus of claim 1, further comprising: a first coating enveloping theat least one ingestible device; and a second coating provided over thefirst coating.
 10. The apparatus of claim 9, wherein the first coatingis configured to protect the ingestible device from moisture and thesecond coating is the food product.
 11. The apparatus of claim 1, wherein the coating is configured to dissolve at a predetermined pH level.12. The apparatus of claim 1, wherein the coating is configured todissolve by an electrical current.
 13. The apparatus of claim 1, furthercomprising a container to contain the food product and the at least oneingestible device; wherein the container further comprises a battery andRFID circuit embedded in the container and the at least one ingestibledevice further comprises a detection circuit.
 14. The apparatus of claim13, wherein the battery is configured to activate the RFID circuit whenthe container is opened and to transmit an RFID signal; and wherein thedetection circuit is configured to receiver the RFID signal and toactivate the at least one ingestible device to generate an electricalcurrent to dissolve the coating.
 15. The apparatus of claim 1, furthercomprising a handle coupled to the food product, the handle comprising abattery and a metal electrode.
 16. The apparatus of claim 1, furthercomprising a flexible container comprising at least one wall separatingtwo chambers, wherein a first chamber comprises the food product and asecond chamber comprises the at least one ingestible device.
 17. Theapparatus of claim 16, wherein the wall is configured to rupture bysqueezing the flexible tube.
 18. The apparatus of claim 1, furthercomprising a thin-film drug delivery mechanism comprising a film thatdissolves when placed in the mouth.
 19. The apparatus of claim 18,wherein the at least one ingestible device is embedded within the film.20. The apparatus of claim 1, wherein the coating is configured todissolve at a predetermined temperature.
 21. The apparatus of claim 1,further comprising an ingestible medication stored within the foodproduct.
 22. The apparatus of claim 1, wherein the ingestible devicecomprises: a support structure; a first material physically associatedwith the support structure; and a second material physically associatedwith the support structure at a location different from the location ofthe first material, such that the first material and second material areelectrically isolated from each other and capable of generating avoltage potential when in contact with a conducting fluid, wherein thesupport structure includes a control module for controlling theconductance between the first material and the second material; andwherein the ingestible device is activated when in contact with theconducting fluid and the contact results in a current signature thatincludes information encoded therein using the control module.
 23. Asystem, comprising: a food product; at least one ingestible deviceassociated with the food product to communicate information, theingestible device associated with an ingestible medication to beingested in conjunction with the food product; at least one coatingmaterial surrounding the at least one ingestible device; wherein thecoating is configured to release the at least one ingestible device uponthe occurrence of an event; and an acoustic receiver configured tocouple to a user, the acoustic receiver configured to detect acousticsounds emanating from a body of a user.
 24. The system of claim 23,wherein the acoustic sounds are generated by masticating the foodproduct.
 25. The system of claim 23, further comprising a piezoelectricelement electrically coupled to ingestible device.